The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities - including sodium-glucose cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption - as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease

From a global perspective, the large and diverse African population is disproportionately affected by cardiovascular disease (CVD). The historical balance between communicable and noncommunicable pathways to CVD in different African regions is dependent on external factors over the life course and at a societal level. The future risk of noncommunicable forms of CVD (predominantly driven by increased rates of hypertension, smoking, and obesity) is a growing public health concern. The incidence of previously rare forms of CVD such as coronary artery disease will increase, in concert with historically prevalent forms of disease, such as rheumatic heart disease, that are yet to be optimally prevented or treated. The success of any strategies designed to reduce the evolving and increasing burden of CVD across the heterogeneous communities living on the African continent will be dependent upon accurate and up-to-date epidemiological data on the cardiovascular profile of every major populace and region. In this Review, we provide a contemporary picture of the epidemiology of CVD in Africa, highlight key regional discrepancies among populations, and emphasize what is currently known and, more importantly, what is still unknown about the CVD burden among the >1 billion people living on the continent.

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Cardiovascular disease in Africa: epidemiological profile and challenges

Stem cells are a relevant source of information about cellular differentiation, molecular processes and tissue homeostasis, but also one of the most putative biological tools to treat degenerative diseases. This review focuses on human stem cells clinical and experimental applications. Our aim is to take a correct view of the available stem cell subtypes and their rational use in the medical area, with a specific focus on their therapeutic benefits and side effects. We have reviewed the main clinical trials dividing them basing on their clinical applications, and taking into account the ethical issue associated with the stem cell therapy.

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Stem cells in clinical practice: applications and warnings.

Diabetic nephropathy (DN) is one of the most important long-term complications of diabetes. Patients with diabetes and chronic kidney disease have an increased risk of all-cause mortality, cardiovascular mortality, and kidney failure. The clinical diagnosis of DN depends on the detection of microalbuminuria. This usually occurs after the first five years from the onset of diabetes, and predictors of DN development and progression are being studied but are not yet implemented into clinical practice. Diagnostic tests are useful tools to recognize onset, progression and response to therapeutic interventions. Microalbuminuria is an indicator of DN, and it is considered the only noninvasive marker of early onset. However, up to now there is no diagnostic tool that can predict which patients will develop DN before any damage is present. Pathological renal injury is hard to predict only with clinical and laboratory findings. An accurate estimate of damage in DN can only be achieved by the histological analysis of tissue samples. At the present time, renal biopsy is indicated on patients with diabetes under the suspicion of the presence of nephropathies other than DN. Results from renal biopsies in patients with diabetes had made possible the classification of renal biopsies in three major groups associated with different prognostic features: diabetic nephropathy, non-diabetic renal disease (NDRD), and a superimposed non-diabetic condition on underlying diabetic nephropathy. In patients with type 2 diabetes with a higher degree of suspicion for NDRD, it is granted the need of a renal biopsy. It is important to identify and differentiate these pathologies at an early stage in order to prevent progression and potential complications. Therefore, a more extensive use of biopsy is advisable.

Diabetic nephropathy: Is it time yet for routine kidney biopsy?

Background. The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, in many cases, they are rather developing a nondiabetic renal disease (NDRD) or mixed forms (DN + NDRD). 
Methods. We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by meta-analysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. 
Results. In the 48 included studies (n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Meta-regression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. 
Conclusions. NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients who might benefit from biopsy.

Renal biopsy in patients with diabetes : a pooled meta-analysis of 48 studies

Background: Cutaneous manifestations occurring in patients with end stage renal failure on hemodialysis are polymorphic and diverse. Objective: The aim of our study was to assess the prevalence and characteristics of different cutaneous manifestations in patients on hemodialysis. Patients and methods: We led a transverse investigation of all patients on hemodialysis in 12 haemodialysis centres of Sfax (Tunisia). We examined 458 patients (254 men and 204 women). The hemodialysis history ranged from 6 months to 24 years. A total of 394/458 (86%) patients had cutaneous abnormalities. These included pruritus (56.6% of patients), paleness (60.7%), xerosis (52.8%), hyperpigmentation or hypopigmentation (38.4%), venous dilation near the fistula (22.2%), eczema in the fistula area (14.8%), half-and-half nails (13.5%), onychodystrophy (6.1%), subungual hemorrhage (4.5%), leukonychia (4.5%), stomatitis (5.6%), xerostomia (3.2%), gingivitis (2.4%), uremic breath (2.1%), and skin calcificatins (0.4%). Nephrogenic fibrosing dermopathy was not detected in any of our patients. Conclusion: Pruritus, paleness, dry skin as well as hyperpigmentation and hypopigmentation are the most frequent skin abnormalities observed in hemodialysis patients. The early recognition of some cutaneous conditions associated with end stage renal failure and hemodialysis may allow early therapeutic intervention and decrease morbidity. ( J Dermatol Case Rep . 2014; 8(4): 86-94)

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Cutaneous abnormalities in patients with end stage renal failure on chronic hemodialysis. A study of 458 patients.

The occurrence of renal involvement during the clinical course of systemic lupus erythematous (SLE) is generally considered to be the most important factor influencing the prognosis in terms of morbidity and mortality. The factors influencing prognosis in lupus nephritis (LN) are variable in literature. Our aim was to determine predictive factors of poor prognosis in LN among our population. In this retrospective study, 82 cases of LN observed over 18 years were studied. There were 12 males and 70 females with a mean age of 26.9 ± 11 years. At presentation, the mean proteinuria was 3.9 ± 4 g/day; the nephrotic syndrome, hematuria, leukocyturia and renal failure were observed in 67.1%, 63.4%, 56.1% and 37.8% of cases, respectively. LN was of class I, II, III, IV and V in 4.9%, 13.4%, 23.2%, 50% and 8.5% of the cases, respectively. Fifteen patients developed end-stage renal failure and/or died. The presence of hypertension, renal failure, massive proteinuria and high activity index score of LN was associated with poor renal prognosis.

Poor prognostic factors of lupus nephritis.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal antiinflammatory drug.

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Ciprofloxacin-induced crystal nephropathy.

The objective of this study was to determine the main clinical and laboratory features as well as the morbidity and mortality of systemic lupus erythematosus (SLE) in a population of patients predominantly from the south of Tunisia. A retrospective review of a well documented population of 146 patients with SLE was undertaken. All patients fulfilled four or more criteria defined by the American College of Rheumatology. The mean age at presentation was 29.2 years (range 6-55) and the mean duration of follow-up was 62 months (range 0.25-374). Musculoskeletal (84.2%) and mucocutaneous (75.3%) were the most frequent clinical manifestations. Antinuclear antibodies were detected in 97.3%, anti-DNA antibodies in 69.2% and anti-Sm in 39.2% of the patients. Anti-cardiolipin antibodies and lupus anticoagulant were ob-served respectively in 71.6% and 37.8% of the patients. The five-year survival rate in our series was 92%. Renal involvement and thrombocytopenia were associated with poor prognosis (p< 0.05). The clinical and immunological characteristics of our SLE patients are largely comparable to most major studies. Main differences included prominent major organ damage and high pre-valence of anti-Sm and anti-cardiolipin antibodies.

Clinical and immunological manifestations of systemic lupus erythematosus: study on 146 south Tunisian patients.

Renal involvement is rarely reported and little is known about the renal morphologic changes in the idiopathic hypereosinophilic syndromes. We reported a case of a 52-year-old man with idiopathic hypereosinophilic syndrome associated with membranous glomerulopathy. The eosinophilia and the proteinuria greatly improved with corticosteroid treatment. We review the literature regarding the nephropathy of this hematologic disorder.

Mohamed Ben Hmida

Papers

Cutaneous abnormalities in patients with end stage renal failure on chronic hemodialysis. A study of 458 patients.

Poor prognostic factors of lupus nephritis.

Ciprofloxacin-induced crystal nephropathy.

Clinical and immunological manifestations of systemic lupus erythematosus: study on 146 south Tunisian patients.

Membranous glomerulopathy associated with idiopathic hypereosinophilic syndrome.