Showing papers in "Ndt Plus in 2018"

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2016: a summary.

Abstract: Background This article summarizes the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry's 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. Methods In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. Results In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006-10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9-50.1).

The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study

Abstract: Diabetes is a common cause of chronic kidney disease (CKD), but in aggregate, non-diabetic diseases account for a higher proportion of cases of CKD than diabetes in many parts of the world. Inhibition of the renin-angiotensin system reduces the risk of kidney disease progression and treatments that lower blood pressure (BP) or low-density lipoprotein cholesterol reduce cardiovascular (CV) risk in this population. Nevertheless, despite such interventions, considerable risks for kidney and CV complications remain. Recently, large placebo-controlled outcome trials have shown that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce the risk of CV disease (including CV death and hospitalization for heart failure) in people with type 2 diabetes who are at high risk of atherosclerotic disease, and these effects were largely independent of improvements in hyperglycaemia, BP and body weight. In the kidney, increased sodium delivery to the macula densa mediated by SGLT-2 inhibition has the potential to reduce intraglomerular pressure, which may explain why SGLT-2 inhibitors reduce albuminuria and appear to slow kidney function decline in people with diabetes. Importantly, in the trials completed to date, these benefits appeared to be maintained at lower levels of kidney function, despite attenuation of glycosuric effects, and did not appear to be dependent on ambient hyperglycaemia. There is therefore a rationale for studying the cardio-renal effects of SGLT-2 inhibition in people at risk of CV disease and hyperfiltration (i.e. those with substantially reduced nephron mass and/or albuminuria), irrespective of whether they have diabetes.

A comparative analysis of survival of patients on dialysis and after kidney transplantation.

Abstract: Background Kidney transplant survival benefits are not observed for around 8 months after transplantation because of a higher complications rate in early post-transplant periods. This study compares survival of patients awaiting transplantation with survival of transplant recipients and non-listed dialysis patients in Ireland. Methods In this retrospective analysis, the relative-risk (RR) of death was assessed with time-dependent, non-proportional hazards analysis, with adjustment for age, cause of end-stage kidney disease (ESKD), time from first treatment for ESKD to placement on the waiting list and year of initial placement on the list. Results A total of 3597 patients were included. Annual death rates per 100 patient-years at risk for all patients on dialysis, waiting-list patients and transplant recipients were 16.5, 2.4 and 1.2, respectively. Death rate was highest among diabetics. The relative risk of death for all patients on dialysis was five times higher than the waiting-list patients [RR, 4.90; 95% confidence interval (CI), 3.70-6.52; P < 0.001]. Time to survival equilibration was 1 year. Thereafter, the 5-year mortality risk was estimated to be 47% lower than that of the patients on the waiting list (RR, 0.53; 95% CI, 0.37-0.77; P = 0.001). Conclusions Transplant recipients had a higher risk of death initially, but a better long-term survival. Time to death risk equilibration was longer compared with other studies. This could be explained by better survival rates in our waiting-list cohort.

Frailty and chronic kidney disease: current evidence and continuing uncertainties

Abstract: Frailty, the state of increased vulnerability to physical stressors as a result of progressive and sustained degeneration in multiple physiological systems, is common in those with chronic kidney disease (CKD). In fact, the prevalence of frailty in the older adult population is reported to be 11%, whereas the prevalence of frailty has been reported to be greater than 60% in dialysis-dependent CKD patients. Frailty is independently linked with adverse clinical outcomes in all stages of CKD and has been repeatedly shown to be associated with an increased risk of mortality and hospitalization. In recent years there have been efforts to create an operationalized definition of frailty to aid its diagnosis and to categorize its severity. Two principal concepts are described, namely the Fried Phenotype Model of Physical Frailty and the Cumulative Deficit Model of Frailty. There is no agreement on which frailty assessment approach is superior, therefore, for the time being, emphasis should be placed on any efforts to identify frailty. Recognizing frailty should prompt a holistic assessment of the patient to address risk factors that may exacerbate its progression and to ensure that the patient has appropriate psychological and social support. Adequate nutritional intake is essential and individualized exercise programmes should be offered. The acknowledgement of frailty should prompt discussions that explore the future care wishes of these vulnerable patients. With further study, nephrologists may be able to use frailty assessments to inform discussions with patients about the initiation of renal replacement therapy.

Risk factors associated with post–kidney transplant malignancies: an article from the Cancer-Kidney International Network

Abstract: In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.

What do epidemiological studies tell us about chronic kidney disease of undetermined cause in Meso-America? A systematic review and meta-analysis.

Abstract: Background: The aim of this systematic review is to examine the epidemiological knowledge and gaps in understanding of the potential causes of chronic kidney disease of undetermined cause (CKDu) in Meso-America. // Methods: A systematic literature search of epidemiological studies of CKDu was conducted in PubMed, Embase and Web of Science from January 2000 to January 2017. Study quality was assessed by adapting the tool from Higgins et al. for observational studies. Where applicable, the summary prevalence odds ratio (POR) and 95% confidence interval (CI) were calculated using a random effects model. // Results: Twenty-five epidemiological studies were included in the analysis of risk factors for CKDu. The quality assessment of each occupational and community study was medium. The PORs for CKDu were males versus females 2.42 (95% CI 1.76–3.08), family history of CKD (versus none) 1.84 (95% CI 1.37–2.30), high water intake (versus low) 1.61 (95% CI 1.01–2.21) and low altitude (versus highland) 2.09 (95% CI 1.00–3.17). There were no significant associations between CKDu and pesticide exposure (versus no) 1.17 (95% CI 0.87–1.46), alcohol consumption (versus no) 1.34 (95% CI 0.84–1.84), non-steroidal anti-inflammatory drugs (versus no) 0.99 (95% CI 0.60–1.39) and heat stress (versus no) 1.52 (95% CI −0.91 – 3.95). // Conclusion: Our meta-analysis showed positive associations for males (versus females) and family history of CKD, water intake, lowland altitude and CKDu. There were no significant associations with pesticide exposure, non-steroidal anti-inflammatory drugs intake, heat stress and alcohol consumption.

Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.

Abstract: Background Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF. Methods In this crossover study, 18 prevalent HD patients were studied in three single mid-week dialysis treatments during three consecutive weeks as follows: first week with OL-HDF with a standard HF dialyser, second week with conventional HD with a standard HF dialyser and third week with conventional HD with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and albumin losses were collected for the different dialysers. Results MCO HD provided a greater reduction of middle and larger middle molecules compared with standard HF HD [rate reduction (RR) β2-microglobulin 74.7% versus 69.7%, P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%, P=0.001; RR α1-glycoprotein 2.8% versus -0.1%, P=0.01]. We found no difference in the clearance of small and larger middle molecules comparing MCO HD with OL-HDF. Albumin losses were 0.03 g/session with MCO HD and 3.1 g/session with OL-HDF (P=0.001). Conclusion MCO HD is superior to standard HF HD in the removal of middle and larger middle molecules and it is not inferior to OL-HDF in the clearance of small and larger middle molecules. Thus it could be an alternative in patients in which it is not possible to perform OL-HDF.

Adherence to medication in patients with chronic kidney disease: a systematic review of qualitative research.

Abstract: Non-adherence to multipharmacological treatment increases the risk of morbidity, mortality and hospitalization. We know little about the perspective of patients with chronic kidney disease regarding factors influencing medicine taking. This study aimed to synthesize findings from qualitative studies of patients' experiences of factors that facilitate and hinder adherence to medication. A systematic review of qualitative studies adhering to the Enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) framework. Systematic searches were conducted in several databases. We used thematic synthesis and the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) approach to assess the confidence of the evidence. Nineteen studies involving 381 patients with chronic kidney disease were included. We identified three analytical themes; logistics, benchmarking the need for medication; and the quality of the patient-physician relationship, with seven descriptive sub-themes as factors influencing patients' adherence to medications. Helping patients to map their everyday activities and motivating them to associate medications with everyday activities may facilitate adherence to medications. Addressing patient beliefs about medications, supporting patients in coping with side effects of medications and eliciting patients' wishes for involvement in treatment decisions may also facilitate adherence. Barriers to adherence were the costs of buying medications, and lacking understanding of the indications and effects of medications. The findings in this synthesis resonate with previous research and extend the known literature by synthesizing and formally assessing confidence in the evidence.

Clinical and diagnostic features of Bartter and Gitelman syndromes.

Abstract: Background: Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform prognosis and management. / Methods: Long-term longitudinal data were analysed for 45 children with pathogenic variants in SLC12A1 (n = 8), KCNJ1 (n = 8), CLCNKB (n = 17), BSND (n = 2) and SLC12A3 (n = 10) seen at a single centre between 1984 and 2014. Median follow-up was 8.9 [interquartile range (IQR) 0.7–18.1] years. / Results: Polyhydramnios and prematurity were seen in children with SLC12A1 and KCNJ1 mutations. Patients with CLCNKB mutations had the lowest serum potassium and serum magnesium and the highest serum bicarbonate levels. Fractional excretion of chloride was >0.5% in all patients prior to supplementation. Nephrocalcinosis at presentation was present in the majority of patients with SLC12A1 and KCNJ1 mutations, while it was only present in one patient with CLCNKB and not in SLC12A3 or BSND mutations. Growth was impaired, but within the normal range (median height standard deviation score −1.2 at the last follow-up). Impaired estimated glomerular filtration rate (eGFR <90 mL/min/1.73 m2) at the last follow-up was seen predominantly with SLC12A1 [71 mL/min/1.73 m2 (IQR 46–74)] and KCNJ1 [62 mL/min/1.73 m2 (IQR 48–72)] mutations. Pathological albuminuria was detected in 31/45 children. / Conclusions: Patients with Bartter and Gitelman syndromes had a satisfactory prognosis during childhood. However, decreased eGFR and pathologic proteinuria was evident in a large number of these patients, highlighting the need to monitor glomerular as well as tubular function. Electrolyte abnormalities were most severe in CLCNKB mutations both at presentation and during follow-up. Fractional excretion of chloride prior to supplementation is a useful screening investigation in children with hypokalaemic alkalosis to establish renal salt wasting.

Clinical and pathological phenotype of genetic causes of focal segmental glomerulosclerosis in adults.

Abstract: Focal segmental glomerulosclerosis (FSGS) is a histologic lesion resulting from a variety of pathogenic processes that cause injury to the podocytes. Recently, mutations in more than 50 genes expressed in podocyte or glomerular basement membrane were identified as causing genetic forms of FSGS, the majority of which are characterized by onset in childhood. The prevalence of adult-onset genetic FSGS is likely to be underestimated and its clinical and histological features have not been clearly described. A small number of studies of adult-onset genetic FSGS showed that there is heterogeneity in clinical and histological findings, with a presentation ranging from sub-nephrotic proteinuria to full nephrotic syndrome. A careful evaluation of adult-onset FSGS that do not have typical features of primary or secondary FSGS (familial cases, resistance to immunosuppression and absence of evident cause of secondary FSGS) should include a genetic evaluation. Indeed, recognizing genetic forms of adult-onset FSGS is of the utmost importance, given that this diagnosis will have major implications on treatment strategies, selecting of living-related kidney donor and renal transplantation success.

Cost of hemodialysis in a public sector tertiary hospital of India

Abstract: Introduction Nearly 220000 patients are diagnosed with end-stage renal disease (ESRD) every year, which calls for an additional demand of 34 million dialysis sessions in India. The government of India has announced a National Dialysis Programme to provide for free dialysis in public hospitals. In this article we estimate the overall cost of performing hemodialysis (HD) in a tertiary care hospital. Second, we assess the catastrophic impact of out-of-pocket expenditures (OOPEs) for HD on households and its determinants. Methods The economic health system cost of HD was estimated using bottom-up costing methods. All resources, capital and recurrent, utilized for service delivery from April 2015 to March 2016 were identified, measured and valued. Capital costs were annualized after accounting for their useful life and discounting at 3% for future years. Sensitivity analyses were undertaken to determine the effect of variation in the input prices and other assumptions on the annual health system cost. OOPEs were assessed by interviewing 108 patients undergoing HD in the study hospital to account for costs from the patient's perspective. The prevalence of catastrophic health expenditures (CHEs) was computed per threshold of 40% of non-food expenditures. Results The overall average cost incurred by the health system per HD session was INR 4148 (US$64). Adjusting for capacity utilization, the health system incurred INR 3025 (US$47) per HD at 100% bed occupancy. The mean OOPE per patient per session was INR 2838 (US$44; 95% confidence interval US$34-55). The major components of this OOPE were medicines and consumables (64.1%). The prevalence of a CHE per HD session was 11.1%. Conclusion Our study findings would be useful in the context of planning for dialysis services, setting provider payment rates for dialysis under various publicly sponsored health insurance schemes and undertaking future cost-effectiveness analysis to guide resource allocation decisions.

Capillary rarefaction from the kidney point of view.

Abstract: Capillary rarefaction is broadly defined as a reduction in vascular density. Capillary rarefaction in the kidneys is thought to promote hypoxia, impair hemodynamic responses and predispose to chronic kidney disease (CKD) progression and hypertension development. Various mechanisms have been suggested to play a role in the development of capillary rarefaction, including inflammation, an altered endothelial-tubular epithelial cell crosstalk, a relative deficiency in angiogenic growth factors, loss of pericytes, increased activity of Transforming growth factor -β1 and thrombospondin-1, vitamin D deficiency, a link to lymphatic neoangiogenesis and INK4a/ARF (Cylin-dependent kinase inhibitor 2a; CDKN2A). In this review, we summarize the tools available to monitor capillary rarefaction noninvasively in the clinic, the contribution of capillary rarefaction to CKD and hypertension, the known mechanisms of capillary rarefaction, and potential future strategies to attenuate capillary rarefaction and reduce its negative impact. Therapeutic strategies to be explored in more detail include optimization of antihypertensive therapy, vitamin D receptor activators, sirtuin 1 activators, Hypoxia inducible factor prolyl hydroxylase inhibitors and stem cell therapy.

Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis.

Abstract: Background This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis. Methods Baseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) 50%: HR 7.67 (95% CI 3.75-15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA 50%: HR 13.99 (95% CI 4.91-39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine. Conclusions Interstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.

International Society of Nephrology's 0by25 initiative (zero preventable deaths from acute kidney injury by 2025): focus on diagnosis of acute kidney injury in low-income countries.

Abstract: In developing countries with limited medical infrastructure, preservation and recovery of renal function following acute kidney injury (AKI) is difficult. In conjunction with clinical presentation, rapid measurement of renal function is essential for early diagnosis and management. Especially in low- and middle-income countries, simple interventions such as hydration and avoidance of toxins have the highest probability of recovery. In such contexts, measurement of urine volume and osmolality and serum creatinine with point-of-care devices and saliva urea nitrogen dipsticks can be valuable. This review aims to identify currently available methodologies to assist in reaching the ambitious goal of the 0by25 initiative to eliminate all preventable deaths from AKI by 2025.

Do kidney transplantations save money? – A study using a before–after design and multiple register-based data from Sweden

Abstract: Background: The health care costs of kidney transplantation and dialysis are generally unknown. This study estimates the Swedish health care costs of kidney transplantation and dialysis over 10 years from a health care perspective.Method: A before–after design was used, in which the patients served as their own controls. Health care costs the year before transplantation were assumed to continue in the absence of a transplant and the cost savings was therefore calculated as the difference between the expected costs and the actual costs during the 10-year follow-up period. Factors associated with the size of the cost savings were studied using ordinary least-squares regression.Results: Altogether 66–79% of the expected health care costs over 10 years were avoided through kidney transplantation, resulting in a cost savings of €380 000 (2012 price-year) per patient. Savings were the highest for successful transplantations, but on average the treatment was cost-saving also for patients who returned to dialysis. No gender or age differences could be found, with the exception of a higher cost of transplantation for children and a generally higher cost for younger compared with older patients on dialysis. A negative association was also found between age at the time of transplantation and the size of the cost savings for the younger part of the sample.Conclusion: Kidney transplantations have led to substantial cost savings for the Swedish health care system. An increase in donated kidneys has the potential to further reduce the cost of renal replacement therapy. (Less)

Porphyria and kidney diseases.

Abstract: The kidneys, after the bone marrow and liver, are third in terms of the amounts of haem synthesized daily. Haem is incorporated into haemoproteins that are critical to renal physiology. In turn, disturbances in haem metabolism interfere with renal physiology and are tightly interrelated with kidney diseases. Acute intermittent porphyria causes kidney injury, whereas medical situations associated with end-stage renal disease, such as porphyrin accumulation, iron overload and hepatitis C, participate in the inhibition of uroporphyrinogen decarboxylase and predispose the individual to porphyria cutanea tarda. Even if some of these interactions have been known for a long time, the clinical situations associated with these interrelations have strikingly evolved over time with the advent of new therapeutic strategies for dialysis therapy and a better understanding of the pathophysiological mechanisms of porphyria-associated kidney disease. Physicians should be aware of these interactions. The aim of this review is to summarize the complex interactions between kidney physiology and pathology in the settings of porphyria and to emphasize their often-underestimated importance.

Comparison of native and transplant kidney biopsies: diagnostic yield and complications.

Abstract: Background The safety and adequacy are established for the native percutaneous renal biopsy (PRB) but no prospective studies exist that directly compare these with transplant PRB Methods From 1995 to 2015, 1705 adults underwent percutaneous native [native renal biopsy (NRB)] or transplant renal biopsy (TRB) by the Nephrology service Real-time ultrasound and automated biopsy needles (NRB, 14 or 16 gauge; TRB, 16 gauge) were used Patients were observed for 24 h (NRB) or 8 h (TRB) post-procedure Adequacy was defined as tissue required for diagnosis plus glomerular yield Complications were defined as those resulting in the need for an intervention, such as surgery, interventional radiologic procedure, readmission, blood transfusion and death Data were collected prospectively in all biopsies Results At the time of biopsy, NRB patients were younger (mean ± SD, 47 ± 17 versus 50 ± 14 years, P 99% of NRB and TRB (P = 071) Compared with TRB, NRB had a greater drop in Hgb after the biopsy (097 ± 11 versus 073 ± 13 g/dL, P < 00001), a higher complication rate (65 versus 39%, P = 002) and higher transfusion rate (52 versus 33%, P = 0045) There was one death in each group attributed to the biopsy Conclusions Although death is equally rare, the complication rate is higher in NRB compared with TRB despite TRB having more of the traditional risk factors for bleeding Differences in technique, operator (fellow or attending) or needle gauge may explain this variability

Chronic kidney disease: considerations for monitoring skeletal muscle health and prescribing resistance exercise.

Abstract: Skeletal muscle wasting has gained interest as a primary consequence of chronic kidney disease (CKD) due to the relationship between skeletal muscle mass, mortality and major adverse cardiovascular events in this population. The combination of reductions in physical function, skeletal muscle performance and skeletal muscle mass places individuals with CKD at greater risk of sarcopenia. Therefore the monitoring of skeletal muscle composition and function may provide clinical insight into disease progression. Dual-energy X-ray absorptiometry and bioelectrical impedance analysis are frequently used to estimate body composition in people with CKD within clinical research environments, however, their translation into clinical practice has been limited. Proxy measures of skeletal muscle quality can be obtained using diagnostic ultrasound, providing a cost-effective and accessible imaging modality to aid further clinical research regarding changes in muscle composition. Clinicians and practitioners should evaluate the strengths and limitations of the available technology to determine which devices are most appropriate given their respective circumstances. Progressive resistance exercise has been shown to improve skeletal muscle hypertrophy of the lower extremities, muscular strength and health-related quality of life in end-stage renal disease, with limited evidence available in CKD predialysis. Fundamental principles (i.e. specificity, overload, variation, reversibility, individuality) can be used in the development of more advanced programs focused on improving specific neuromuscular and functional outcomes. Future research is needed to determine the applicability of skeletal muscle monitoring in clinical settings and the feasibility and efficacy of more advanced resistance exercise approaches in those with CKD predialysis.

Patterns of progression of chronic kidney disease at later stages.

Abstract: Background At later stages of chronic kidney disease (CKD), a pattern of linear and irreversible renal function decline is thought to be the most common. The objective of this study was to describe the characteristics of the different patterns of CKD progression, and to investigate potentially modifiable factors associated with the rate of decline of renal function. Methods This was a retrospective, observational study in a cohort of adult patients with CKD Stage 4 or 5 not on dialysis. Decline in renal function was estimated as the slope of the individual linear regression line of estimated glomerular filtration rate (eGFR) over time. The following patterns of CKD progression were considered: unidentifiable, linear, nonlinear (curvilinear) and positive (improvement of renal function). Results The study group consisted of 915 patients (mean ±SD age 65 ± 14 years, 48% females, median follow-up time 16 months). A linear pattern was observed in 38%, unidentifiable in 23%, nonlinear in 24% and positive in 15% of the study patients. The mean eGFR slope was: -3.35 ± 4.45 mL/min/year. Linear and unidentifiable patterns were associated with more rapid loss of renal function. By multiple linear and logistic regression analysis, the magnitude of proteinuria, the systolic blood pressure and the treatment with dual renin-angiotensin system blockade were associated with more rapid CKD progression. On the contrary, older age and discontinuation of commonly prescribed medication with potential influence on renal function or eGFR measurements were associated with slower CKD progression. Conclusions A majority of patients with advanced CKD show patterns of renal function decline different from linear, and several of the main determinants of CKD progression are potentially modifiable.

Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1.

Abstract: Little is known about the molecular pathogenesis of congenital nephrotic syndrome in association with primary adrenal insufficiency. Most recently, three groups found concurrently the underlying genetic defect in the gene sphingosine-1-phosphate lyase 1 (SGPL1) and called the disease nephrotic syndrome type 14 (NPHS14). In this report we have performed whole-exome sequencing and identified a new homozygous variant in SGPL1, p.Arg340Trp, in a girl with nephrotic syndrome and Addison's disease. Her brother died previously with the same phenotype and hyperpigmentation of the skin. We reviewed the reported cases and concluded that NPHS14 is a clinically recognizable syndrome. The discovery of this syndrome may contribute to the diagnosis and description of additional patients who could benefit from treatment, genetic counseling and screening for related comorbidities. Until now, patients with congenital nephrotic syndrome associated with primary adrenal insufficiency have been treated as having two different diseases; however, the treatment for patients with NPHS14 should be unique, possibly targeting the sphingolipid metabolism.

Renal involvement in chronic lymphocytic leukemia.

Abstract: Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult leukemia in the USA and Western Europe. Kidney disease can present in patients with CLL as a manifestation of the disease process such as acute kidney injury with infiltration or with a paraneoplastic glomerular disease or as a manifestation of extra renal obstruction and tumor lysis syndrome. In the current era of novel targeted therapies, kidney disease can also present as a complication of treatment. Tumor lysis syndrome associated with novel agents such as the B-cell lymphoma 2 inhibitor venetoclax and the monoclonal antibody obinutuzumab are important nephrotoxicities associated with these agents. Here we review the various forms of kidney diseases associated with CLL and its therapies.

Management of autosomal-dominant polycystic kidney disease-state-of-the-art.

Abstract: Autosomal-dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of end-stage renal disease in adults. Affected individuals and families face a significant medical and psychosocial burden due to both renal and extrarenal manifestations. Consequently, interventions that ameliorate the course of the disease and specifically slow down the loss of kidney function are of special interest. Major research efforts in both the clinical and pre-clinical setting in the last two decades resulted in a number of pivotal clinical trials aimed to ameliorate the disease. These studies have underlined the important role of specific supportive measures and provided the basis for first targeted pharmacological therapies. Very recently, the concept of repurposing drugs approved for other conditions for a use in ADPKD has gained increasing attention. Here, we review the current best-practice management of ADPKD patients with a focus on interventions that have reached clinical use to maintain kidney function and give an outlook on future trials and potential novel treatment strategies.

Old and new calcimimetics for treatment of secondary hyperparathyroidism: impact on biochemical and relevant clinical outcomes

Abstract: Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, and cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress parathyroid hormone (PTH) secretion, while also promoting calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor, so that even with lower levels of extracellular calcium a signal can still exist, leading to a decrease of the set-point for systemic calcium homeostasis. This enables a decrease in plasma PTH levels and, consequently, of calcium levels. Cinacalcet was the first calcimimetic to be approved for clinical use. More than 10 years since its approval, cinacalcet has been demonstrated to effectively reduce PTH and improve biochemical control of mineral and bone disorders in chronic kidney patients. Three randomized controlled trials have analysed the effects of treatment with cinacalcet on hard clinical outcomes such as vascular calcification, bone histology and cardiovascular mortality and morbidity. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Etelcalcetide is a new second-generation calcimimetic with a pharmacokinetic profile that allows thrice-weekly dosing at the time of haemodialysis. It was recently approved in Europe, and is regarded as a second opportunity to improve outcomes by optimizing treatment for SHPT. In this review, we summarize the impact of cinacalcet with regard to biochemical and clinical outcomes. We also discuss the possible implications of the new calcimimetic etelcalcetide in the quest to improve outcomes.

Risk of percutaneous renal biopsy of native kidneys in the evaluation of acute kidney injury.

Abstract: Background Percutaneous renal biopsy (PRB) of native kidneys (NKs) to better understand and treat acute kidney injury (AKI) is being advocated, but little is known about the risk of complications. Methods We performed a retrospective study of PRB of NKs in 955 adults from 1991 to 2015 at an academic medical center with real-time ultrasound and automated biopsy needles. Patients undergoing PRB for evaluation of AKI (n = 160) were compared with 795 patients biopsied for other reasons (not-AKI) for postbiopsy complications [need for transfusion of packed red blood cells (PRBCs), an interventional radiologic or surgical procedure, readmission or death]. Results Patients biopsied for AKI were older (58 ± 16 versus 44 ± 16 years; P < 0.0001), with a higher serum creatinine (SCr) (4.5 ± 2.7 versus 1.8 ± 1.6 mg/dL; P < 0.0001) and lower hemoglobin (Hgb) (10.4 ± 1.7 versus 12.1 ± 2.1; P < 0.0001) and a greater proportion had an abnormal bleeding time (12.5% versus 7.4%, P 0.04), partial thromboplastin time (15.2% versus 5.3%, P < 0.0001) and/or prothrombin time (27.0% versus 12.8%; P < 0.0001) compared with not-AKI patients. Complications post-PRB were significantly greater in patients biopsied for AKI {11.3% versus 6.7%; P=0.04; odds ratio [OR] 1.78 [95% confidence interval (CI) 1.01-3.12]} with patients biopsied for AKI requiring more blood transfusions (10.0% versus 5.3%; P 0.02; OR 2.04 (95% CI 1.12-3.74)]. By multivariate analysis, baseline features predictive of a complication were increased SCr and decreased Hgb level, as well as female gender and increased systolic blood pressure. Conclusion Patients biopsied for evaluation of AKI are at greater risk of complications due to increased risk factors.

Clinical and pathological characteristics of non-diabetic renal disease in type 2 diabetes patients.

Abstract: Background Renal involvement in type 2 diabetes is mainly due to diabetic nephropathy (DN). Nevertheless, a sizable proportion of diabetic patients could actually have nondiabetic renal diseases (NDRDs) or DN plus NDRDs. This study aimed to explore the pathological features of NDRD in diabetic patients and to assess the predictability of diagnosing NDRD (±DN) versus isolated DN on the basis of clinical parameters. Methods Medical records of type 2 diabetes patients who underwent renal biopsy under suspicion of NDRD from January 2011 through November 2015 were analyzed retrospectively. Results A total of 101 patients were enrolled in this study. The most frequent indication for renal biopsy was recent onset of nephrotic syndrome (41%), followed by rapidly progressive renal failure (29%) and active urinary sediment (21%). On renal biopsy, 51% of patients had isolated DN, 20% had isolated NDRD and 29% had DN plus NDRD. IgA nephropathy was the most common cause of isolated NDRD, whereas acute tubular necrosis (39%) and acute interstitial nephritis (33%) were the main causes of NDRD superimposed on DN. Male gender, short-duration diabetes (<8 years), lower glycated hemoglobin and active urinary sediment (≥10 red and white blood cells per high-power field) were independent predictors of NDRD according to multiple logistic regression analysis. Conclusions Judicious use of renal biopsy revealed NDRD (±DN) in nearly half of type 2 diabetes patients with atypical renal presentation, especially in male patients with well-controlled diabetes, those who have had diabetes for a short duration and those with active urinary sediment.

Chronic kidney disease, kidney transplantation and oxidative stress: a new look to successful kidney transplantation.

Abstract: Oxidative stress plays a key role in the pathophysiological process of uremia and its complications, particularly in cardiovascular disease. The level of oxidative stress markers is known to increase as chronic kidney disease progresses and correlates significantly with the level of renal function. Hemodialysis and peritoneal dialysis are major modes of renal replacement therapy for end-stage renal disease patients, but unfortunately they are also accompanied by increased oxidative stress. Successful kidney transplantation, however, results in near normalization of the antioxidant status and lipid metabolism by eliminating free radicals despite the surge of oxidative stress caused by the surgical procedure and ischemic injury to the organ during the operation. This success is associated with both improved renal function, reduced cardiovascular complications and overall improved morbidity and mortality. Measuring oxidative stress markers such as malondialdehyde is promising in predicting allograft survival and delayed graft function.

Causes and predictors of mortality in biopsy-proven lupus nephritis: the Sarawak experience.

Abstract: Background Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can be fatal if left untreated. The causes and prognostic predictors of mortality in LN have been well studied in developed countries but evidence is lacking for developing countries. The objective of this study was to investigate the causes and predictors of mortality in a cohort of Malaysian patients with biopsy-proven LN. Methods We retrospectively studied all patients with biopsy-proven LN treated in Sarawak General Hospital during the period of 2000-15. Demographic data, clinical features and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of mortality. Results There was a total of 250 patients with 259 renal biopsies available for our analysis. Our patients were of multi-ethnic origins with a female predominance (90%). Their mean ± standard deviation age was 37.7 ± 12.8 years. The patients had a mean disease duration of 135.6 ± 81.9 months. Nephrotic syndrome was the most common presentation (29.6%) and acute renal failure was evident at initial presentation in 16% of patients. Class IV LN was the predominant biopsy class within the cohort (66.8%). The majority of patients achieved remission (81.2%) and had normal renal function (83.9%) at the last follow-up. The 5-, 10-, 15- and 20-year survival rates for our cohort were 93%, 88%, 82% and 77%, respectively. There were 37 deaths (14.8%), of which the main causes were: infection and flare (52.7%), infection alone (25.0%) and other causes (22.3%). Independent predictors of mortality in our cohort of LN patients were: the presence of acute kidney injury at presentation [hazard ratio (HR) 3.41; confidence interval (CI) 1.50-7.76], failure to achieve remission at 1-year post-induction therapy (HR 2.99; CI 1.35-6.65) and non-compliance with treatment (HR 1.89; CI 1.22-2.96). Age, ethnicity, class of LN and type of immunosuppressant used were not predictive of mortality. Conclusions Survival and renal outcomes in our LN cohort were comparable to most LN studies reported worldwide. Both flare and infection remained the main causes of death. The presence of acute renal failure at presentation, failure to achieve remission at 1 year post-treatment and non-compliance with treatment were independent prognostic predictors of mortality in LN.

Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that leads to renal failure in the majority of patients. The very first pharmacological treatment, tolvaptan, received Food and Drug Administration approval in 2018 after previous approval in Europe and other countries. However, tolvaptan is moderately effective and may negatively impact a patient's quality of life due to potentially significant side effects. Additional and improved therapies are still urgently needed, and several clinical trials are underway, which are discussed in the companion paper Muller and Benzing (Management of autosomal-dominant polycystic kidney disease-state-of-the-art) Clin Kidney J 2018; 11: i2-i13. Here, we discuss new therapeutic avenues that are currently being investigated at the preclinical stage. We focus on mammalian target of rapamycin and dual kinase inhibitors, compounds that target inflammation and histone deacetylases, RNA-targeted therapeutic strategies, glucosylceramide synthase inhibitors, compounds that affect the metabolism of renal cysts and dietary restriction. We discuss tissue targeting to renal cysts of small molecules via the folate receptor, and of monoclonal antibodies via the polymeric immunoglobulin receptor. A general problem with potential pharmacological approaches is that the many molecular targets that have been implicated in ADPKD are all widely expressed and carry out important functions in many organs and tissues. Because ADPKD is a slowly progressing, chronic disease, it is likely that any therapy will have to continue over years and decades. Therefore, systemically distributed drugs are likely to lead to potentially prohibitive extra-renal side effects during extended treatment. Tissue targeting to renal cysts of such drugs is one potential way around this problem. The use of dietary, instead of pharmacological, interventions is another.

The metabolomic quest for a biomarker in chronic kidney disease.

Abstract: Chronic kidney disease (CKD) is a growing burden on people and on healthcare for which the diagnostics are niether disease-specific nor indicative of progression. Biomarkers are sought to enable clinicians to offer more appropriate patient-centred treatments, which could come to fruition by using a metabolomics approach. This mini-review highlights the current literature of metabolomics and CKD, and suggests additional factors that need to be considered in this quest for a biomarker, namely the diet and the gut microbiome, for more meaningful advances to be made.

Clinical profile and outcome of pigment-induced nephropathy.

Abstract: Background Pigment nephropathy represents one of the most severe complications of rhabdomyolysis or hemolysis. Methods We performed a retrospective observational study to analyze the etiology, clinical manifestation, laboratory profile and outcome in patients with biopsy-proven pigment-induced nephropathy between January 2011 and December 2016. History, clinical examination findings, laboratory investigations and outcome were recorded. Results A total of 46 patients were included with mean follow-up of 14 ± 5.5 months. Mean age was 40.15 ± 12.3 years, 65% were males (male:female, 1.8:1) and ∼37 (80.4%) had oliguria. Mean serum creatinine at presentation and peak creatinine were 7.5 ± 2.2 and 12.1 ± 4.3 mg/dL, respectively. Evidence of rhabdomyolysis was noted in 26 patients (64%) and hemolysis in 20 patients (36%). Etiology of rhabdomyolysis include snake envenomation (10 patients), seizures (7), strenuous exercise (5), wasp sting (2) and rifampicin induced (2). The causes of hemolysis include rifampicin induced (7 patients), sepsis (5), malaria (3), mismatched blood transfusion/transfusion reaction (3) and paroxysmal nocturnal hemoglobinuria (2). On renal biopsy, two patients had acute interstitial nephritis and two had immunoglobulin A deposits in addition to pigment nephropathy. All except one (97.8%) required hemodialysis (HD) during hospital stay and mean number of HD sessions was 9 ± 2. A total of three patients with sepsis/disseminated intravascular coagulation died, all had associated hemolysis. On statistical analysis, there was no difference between AKI due to rhabdomyolysis and hemolysis except for high creatine phosphokinase in patients with rhabdomyolysis and Lactate dehydrogenase level in patients with hemolysis. At mean follow-up, five patients (12%) progressed to chronic kidney disease (CKD). Conclusions Pigment nephropathy due to rhabdomyolysis and hemolysis is an important cause of renal failure requiring HD. The prognosis was relatively good and depends on the etiology; however, long-term studies and follow-up are needed to assess the true incidence of CKD due to pigment nephropathy.