Fibrosis is a consequence of the inflammatory response. When fibrotic tissue becomes excessive, it can have diverse pathophysiological effects on a number of organ systems. The mechanisms underlying fibrosis and approaches to therapy are reviewed.

https://www.nejm.org/doi/suppl/10.1056/NEJMra1300575/suppl_file/nejmra1300575_appendix.pdf

Fibrosis — A Common Pathway to Organ Injury and Failure

https://www.kidney-international.org/article/S2157-1716(15)32202-4/pdf

Executive summary of the KDIGO Controversies Conference on Supportive Care in Chronic Kidney Disease: developing a roadmap to improving quality care

BACKGROUND
Depression is common in patients with end-stage renal disease (ESRD) and is associated with increased mortality, but little is known about depression in patients just after they start dialysis therapy. We sought to assess the prevalence of depressive symptoms in patients with ESRD starting dialysis therapy, identify patient characteristics associated with depression, and determine whether patients with serious depressive symptoms were receiving treatment.


METHODS
We implemented a multicenter prospective cohort study at 14 dialysis centers in Connecticut. Patients with ESRD who were 18 years and older were interviewed within 10 days of initiating dialysis therapy between November 2000 and July 2001. The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Chi-square tests were used to evaluate associations between several patient characteristics and depression, and multivariable logistic regression models were used to determine odds ratios (ORs) for depression, with adjustment for baseline variables.


RESULTS
Among 123 patients, 44% (54 of 123 patients) had scores above the validated cutoff value in the BDI for depression. In logistic regression analysis, depression was statistically significantly associated with Caucasian race (OR, 3.4; P = 0.02), lower self-rated quality of life (OR, 2.2; P = 0.003), and no previous acquaintances on dialysis therapy (OR, 10.2; P = 0.03). Only 16% (9 of 54 patients) of depressed patients were being treated at enrollment; 13% (5 of 38 patients) of those with mild symptoms and 25% (4 of 16 patients) with more severe symptoms were being treated.


CONCLUSION
Our results show that depressive symptoms are very common at the start of dialysis therapy, and specific characteristics are associated with a greater burden of depressive symptoms. Despite a high prevalence, treatment rates are low, even among patients with moderate to severe symptoms of depression.

The Prevalence and Treatment of Depression Among Patients Starting Dialysis

Background
Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a review first published in 2009.

Objectives
To evaluate the effect of aldosterone antagonists (both selective (eplerenone) and non-selective (spironolactone)) alone or in combination with ACEi or ARB in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including major cardiovascular events, hospitalisation and all-cause mortality; kidney function (proteinuria, glomerular filtration rate (GFR), serum creatinine, and need for renal replacement therapy; and adverse events (including gynaecomastia and hyperkalaemia).

Search methods
For this update, we searched the Cochrane Renal Group's Specialised Register to 30 January 2013 using search terms relevant to this review.

Selection criteria
We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists alone or in combination with ACEi or ARB (or both) with other anti-hypertensive strategies or placebo.

Data collection and analysis
Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We tested for heterogeneity in estimated treatment effects using the Cochran Q test and I² statistic. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals (CI) and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used.

Main results
We identified 27 studies (1549 participants) that were eligible for inclusion. These studies provided no data relating to aldosterone antagonists in addition to ACEi or ARB (or both) on patient-level outcomes including major cardiovascular events and mortality and progression to end-stage kidney disease (ESKD) requiring dialysis or transplantation.

Compared with ACEi or ARB (or both), non-selective aldosterone antagonists (spironolactone) combined with ACEi or ARB (or both) significantly reduced 24-hour protein excretion (11 studies, 596 participants): SMD -0.61, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure (BP) at the end of treatment with additional non-selective aldosterone antagonist therapy (systolic BP (10 studies, 556 participants): MD -3.44 mm Hg, 95% CI -5.05 to -1.83) (diastolic BP (9 studies, 520 participants): MD -1.73 mm Hg, 95% CI -2.83 to -0.62).

However, we found that aldosterone antagonist treatment had imprecise effects at the end of treatment on GFR (9 studies, 528 participants; MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51), doubled the risk of hyperkalaemia (11 studies, 632 patients): RR 2.00, 95% CI 1.25 to 3.20; number needed to treat for an additional harmful outcome (NNTH): 7.2, 95% CI 3.4 to ∞) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (4 studies, 281 patients): RR 5.14, 95% CI 1.14 to 23.23; NNTH: 14.1, 95% CI 8.7 to 37.3).

Most studies enrolled few patients (range 12 to 268) and were powered to observe differences in surrogate end points rather than patient-focused outcomes. Nine studies had a cross-over design and the majority of studies did not adequately report study methods to assess methods and study quality.

Authors' conclusions
Aldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown.

Aldosterone antagonists for preventing the progression of chronic kidney disease.

https://www.ajkd.org/article/S0272-6386(10)01085-1/pdf

Prevalence and Correlates of Self-Reported Sexual Dysfunction in CKD: A Meta-analysis of Observational Studies

Aims. Proteinuria and transforming growth factor β (TGF-β) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-β. Aldosterone may not be inhibited with angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) due to aldosterone escape. We aimed to evaluate the effect of spironolactone on parameters leading to fibrosis. Methods. This prospective study included 30 non-diabetic chronic kidney disease (CKD) patients treated with ACEIs and/or ARBs. The patients were divided into two groups that are similar in terms of demographic parameters. 25 mg of spironolactone was added to group 1 (n = 15) for six months, though it was not administered to group 2 (n = 15). Creatinine (U-Cr), protein (U-Prot), and TGF-β1 (U- TGF-β1) were measured in spot urine sample in the beginning of study and six months later. Results. Twenty-four patients completed the study. There were...

Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disease.

Background. Sleep quality (SQ) is a significant problem in peritoneal dialysis (PD) patients, yet the underlying factors are not well known. In addition, depression and impaired quality of life (QOL) are main problems in PD patients. We measured the SQ and investigated the effect of depression, QOL, and some other factors on SQ in PD patients. Methods. Data were collected from 124 PD patients (59 male, 65 female) in our center. Demographic data and laboratory values were analyzed. All patients were asked to complete the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Index (BDI), and SF-36. Results. Mean age of the patients was 52.6 ± 14.3 year. The prevalence of poor SQ was 43.5%, defined as global PSQI score >5. The prevalence of depression was 25.8%, defined as BDI scores >17. The poor sleepers had higher BDI scores, poor QOL, older age, and lower duration of PD compared to the good sleepers. There was not a difference in hemoglobin, albumin, C-reactive protein, Kt/V, urea, creatinine, lipid par...

https://www.tandfonline.com/doi/pdf/10.1080/08860220802406419

Sleep quality and depression in peritoneal dialysis patients.

Background. Sexual dysfunction (SD) is a common problem in end-stage renal disease (ESRD). In contrast to basic and clinical research in the field of male SD, the sexual problems of women have received relatively little attention and are often under-treated. We evaluated sexual function in female ESRD patients using the validated Female Sexual Function Index (FSFI) and relation with QOL, depression, and some laboratory parameters. Methods. 117 ESRD patients (85 peritoneal dialysis [PD], 32 hemodialysis [HD], mean age 48.5 ± 13.9 years) were enrolled. All patients had been dialyzed (PD or HD) for more than three months. In addition, an age-matched married control group of 48 subjects (mean age 47.1 ± 12.7 years) were enrolled in the study. All patients were asked to complete three questionnaires of the FSFI, Beck Depression Index (BDI) and SF-36. Results. Female sexual dysfunction was found in 80 of the 85 peritoneal dialysis patients (94.1%) and all of the HD patients (100%), but in only 22 subjects of th...

https://www.tandfonline.com/doi/pdf/10.1080/08860220902883012

Female sexual dysfunction in peritoneal dialysis and hemodialysis patients

In recent years, Endothelin-1 (ET- 1), Platelet Activating Factor (PAF) and thromboxane have been considered responsible for the pathogenesis of acute cyclosporine nephrotoxicity (ACN). The aim of this study was to investigate the effects of the PAF antagonist gingko glycosid (EGb 761) on both renal histology and ET-1 and Nitric Oxide (NO) levels in experimental ACN. This study was carried out on 30 albino rabbits, divided into three groups. They were: group A (n=10) the control, group B (n=10), which was given intravenous cyclosporine (15mg/kg/day) and group C (n=10), which was given oral gingko glycosid (2.5mg/kg/day) in addition to cyclosporine. Plasma ET-1 and NO levels and renal histology were investigated in all of the groups. Data analysis was performed by Kruskall-Wallis one-way Anova and Mann Whitney-U tests. Plasma ET-1 levels in groups B and C were higher than in the controls (p<0.0002, p<0.0002, respectively). Plasma NO levels in groups B and C were lower than in the controls (p<0.0002, p<0.0047, respectively). However, group C had high NO levels and low ET-1 levels compared to group B (p<0.004, p<0.0002, respectively). Renal histological findings of ACN were observed in group B, and to a lesser extent in group C. Consequently, it was established that the PAF antagonist Gingko glycosid Egb 761 partially improved both the renal histology and plasma ET-1 and NO levels in experimental ACN.

https://journals.tubitak.gov.tr/medical/issues/sag-00-30-2/sag-30-2-3-98145.pdf

Effects of Gingko Glycosid (EGb 761) on Some Vascular Endothelial Functions and Renal Histology in Rabbits With Acute Cyclosporine Nephrotoxicity

In order to investigate the possible role of HLA-related genetic factors in the pathogenesis of diabetic nephropathy (DN), we determined urinary albumin excretion and HLA-typing in 55 type I diabetic patients who have a duration of diabetes longer than 10 years and have no hypertension or clinical proteinuria, and compared patients with incipient DN to ones without nephropathy with respect to frequen­ cy of HLA-antigens. We found that microalbuminuric patients had higher frequencies of HLA-A2 and 68 antigens than those of normoalbuminuric patients. No significant difference was detected in terms of other HLA-Class I and II antigens. The relative risk of microalbiminuria were found to be 5, 3.5 and 10 times greater in the patients with HLA-A2, B8 and A2+B8 antigens than in the patients without the expression of these antigens, respectively. For the presence of microalbimunira, while HLA-A2 had the highest sensitivity (80%), the combination of HLA-A2-B8 had the highest specificity (96%). In conclusion, these findings suggest that possesing of both HLA-A2 and B8 antigens confers a great genetic predisposition to diabetic nephropathy independent of glycémie state and blood pres­ sure. So, HLA typing may be useful in defining high risk patients for nephropathy in early period of type I diabetes. [Turk J Med Res 1996; 14(2):67-70]

N. Yılmaz Selçuk

Papers

Antifibrotic effects of aldosterone receptor blocker (spironolactone) in patients with chronic kidney disease.

Sleep quality and depression in peritoneal dialysis patients.

Female sexual dysfunction in peritoneal dialysis and hemodialysis patients

Effects of Gingko Glycosid (EGb 761) on Some Vascular Endothelial Functions and Renal Histology in Rabbits With Acute Cyclosporine Nephrotoxicity

The relationship between diabetic nephropathy and human leucocyte antigens in patients with type I diabetes mellitus