Journal de néphrologie et thérapeutique

Kidney podocytes are highly differentiated cells with a complex cellular morphology. They are located inside the glomerulus, a corpuscle of capillaries through which blood is filtered hydrostatically through a high-volume/highdiscrimination filter. Neighboring podocyte Foot Processes (FP) is connected by a specialized cell-cell junction, the Slit Diaphragm (SD), which represents the main size selective filtration barrier in the kidney. The podocyte is an attractive cell for drug targeting due largely to its presence on the epithelial surface of one of the best vascularized organs in the body. Podocytes are exposed to 180 liters of filtered water and solutes each day, with the glomerular basement membrane and fenestrated  glomerular endothelium not likely to be obstacles to small molecule passage. Though no podocyte-specific drugs are presently available, clinical nephrology has taken advantage of the pleitropic effects of a diverse array of therapeutic agents to treat glomerular disease. Glucocorticoids, retinoic acid,  cyclosporine, abatacept, ACTH, thiazolidinedione, angiotensin converting enzyme inhibitors and rituximab have been successfully repurposed from other clinical indications to treat protein uric kidney disease. By different mechanisms these agents all nonspecifically target podocytes to promote their survival under disease conditions. This review summarizes the currently understood mechanistic basis for their use.

Background: Patients with steroid-resistant nephrotic syndrome (SRNS) tend to progress to end-stage renal disease (ESRD). Although the risk of steroid resistance depends mainly on histopathology, other factors, such as cytokines, may contribute to this condition. Cytokine macrophage Migration Inhibitory Factor (MIF) acts to counterregulate glucocorticoids, which have become the main drug therapy for NS. The aim of this study was to evaluate whether raised serum MIF levels represent a potential risk factor for SRNS patients.
Methods: A prospective study was conducted in a multi-centre hospital and school in Medan, Sumatera, Indonesia. A total of 99 subjects were included in the study consisting well child (n=31) and NS patients (n=68). Serum macrophage migration inhibitory factor (MIF) was collected and measured. Patient’s data about demographics, blood pressure, threshold steroid dosage at inclusion, urinary albumin creatinine ratio, plasma angiotensin II and serum MIF were compared between groups.
Results: Majority of subjects showed MIF levels between 10.4 and 31.8 ng/ml. Group SRNS had  significantly higher serum MIF (median 31.9 (14.3-117.2) ng/mL) compared to the levels in group SSNS (median 21.8 (10.4-31.8) ng/mL) and well child (median 24.1 (11.4-31.1) ng/mL. Half of SRNS subjects (n=20) showed higher levels of MIF. In logistic regression analysis, diastolic blood pressure and plasma angiotensin II levels were found to be independently associated with higher serum MIF. There was a weak positive liniear correlation between concentration of MIF serum and angiotensin II plasma.
Conclusions: The serum MIF levels in group SRNS is higher than SSNS and well child. Diastolic blood pressure and plasma angiotensin II levels were found to be independently factors associated with higher MIF serum.

The primary goal of the open label study of Renadyl™ in stage 3 and 4 chronic kidney disease patients was to confirm the safety and tolerability of several doses of Renadyl™ (90, 180, 270 billion colony forming units). Secondary goals were to quantify quality of life improvement, to confirm efficacy in reducing commonly known uremic toxins, and to investigate the effects on several biomarkers of inflammation and oxidative stress. Participants underwent physical examinations and venous blood testing, and completed quality of life questionnaires. Data were analyzed with SAS V9.2. Of 31 subjects, 28 (90%) completed the study (2 lost to follow-up). The primary goal was met, as no significant adverse events were noted during the dose escalation phase. All patients tolerated the maximum dose (note: 1 subject reported nausea upon initial use). The escalation efficacy was shown in statistically significant changes of serum creatinine (months 2 to 6: -0.23 mg/dL, p<0.05), C-reactive protein (months 2 to 6: -0.28 mg/L, p<0.05), and hemoglobin (base to month 6: 0.35 mg/dL, p<0.01, months 1 to 6: 0.46 mg/dL, p<0.001, months 2 to 6: 0.58 mg/dL, p<0.0001). Trends, but not statistical significance, were noted in blood urea nitrogen (base to month 4: -3.56 mg/dL, p<0.09; months 1 to 4: -3.81 mg/dL, p<0.07). The secondary goal was also met, as QOL measure of physical functioning improved (base to month 6, p<0.05) and a strong trend in reduction of pain was observed (base to month 6, p<0.08).

Background: The risks associated with performing a percutaneous renal biopsy have substantially decreased in the past two decades because of technical advances in the method. However, bleeding complications still occur, resulting in increased hospital stay, treatment costs and even mortality.
Objective: The purpose of this case reporting is to discuss about life threatening complication like perinephric hematoma following a renal biopsy in a high risk patient with severe renal failure.
Methods: The clinical, radiological findings, prognosis of a massive perinephric hematoma following a renal biopsy in a high risk patient with severe renal failure are discussed.
Results: We report a case of 39 year old, male, non-diabetic, hypertensive since 5 years who presented with unexplained severe renal failure. After dialyzing adequately, he was subjected to right renal biopsy using real time ultrasound guided automated renal biopsy gun. Post biopsy was uneventful, until 72 hours when he developed massive right perinephric hematoma following a heparin-free hemodialysis. He continued to be hypotensive despite hemostatics, blood products, and plasma expander transfusion. Unfortunately, he expired before definitive management like renal angiogram and intervention was attempted.
Conclusions: To the best of our knowledge, this is one of few reports of the occurrence of life threatening
complication like perinephric hematoma in a patient with severe renal failure on heparin free  hemodialysis 72 hours following a renal biopsy.

Dyslipidemia is common in chronic kidney disease patients and alterations in serum lipid profile vary widely depending on the level of kidney function. We studied two hundred Iraqi patients who were diagnosed as having chronic kidney disease from June 2011 to January 2013. They were given erythropoietin for seven months. One hundred sixty patients (80%) showed response to treatment with an improvement in lipid profile, while the other 40 patients (20%) showed no significant response to treatment. In conclusion, treatment with erythropoietin seems to positively influence the lipid profile in patients with chronic kidney disease.

Background: The main objectives of this clinical case presentation were to determine the real cause of a young hypertensive pregnant patient.
Methods: I present the clinical case of a young women patient age 21, pregnant in 32 weeks, which came for a consult because she had headache, dizziness and bilateral symmetric white and soft oedema of the legs. Her blood pressure value was determined as being BP=220/130 mmHg. The urinary examination had shown a proteinuria 20 g/dl. A hypotensive treatment was innitiated with allowed medication during the pregnancy, but the blood pressure values do not completely normalize BP=160/90 mmHg. Because the patient had bilateral lumbar pains an abdominal ultrasound was performed, although innitialy these symptoms were interpreted as being linked to the pregnancy, and surprisingly
a left renal tumor formation of 4,5/3,5 cm was discovered. The plasma renin level was determined as being 198 ng/ ml because of the excess secretion of this substance by the renal cell tumour. The presence of the proteinuria and the lumbar pains should not be interpreted only within the pregnancy context, as these could have also other causes, as the renal cell tumour just like in the above mentioned case. After the patient had given birth, an abdominal CT was performed and confirmed the presence of the right kidney tumor and also a i.v. Urography was performed and showed lacuna image at the level of the right kidney. After the patient had given birth, a right nephrectomy was performed ,and the histopathological examination from the tumour formation that has been extracted and releaved clear cell renal carcinoma.
Results: The presence of the arterial hypertension and proteinuria is difficult to interpretation in context of pregnancy. Usually, in the last weeks of the pregnancy presence of the proteinuria and high blood pressure and bilateral symmetric white and soft oedema of the legs should not be interpreted only within the pregnancy context, as these could have also other causes, as the renal cell tumour just like in the above mentioned case.
Conclusions: The plasma renin level must be performed as a screening test in young pregnant patients, because the blood pressure, as a real cancer marker can draw the attention upon a renal cell tumour diagnosis, not being interpreted only as high blood pressure in the pregnancy context as possible preeclampsia-eclampsia imminence.

Objective: To study the pattern and outcome of acute renal failure (ARF) in diabetes mellitus.
Methods: Outcome of variables like duration of renal failure, recovery of renal function and mortality were analyzed with parameters like age, sex, duration of diabetes mellitus, preexisting diabetic nephropathy, preexisting ischemic heart disease, cause of renal failure, dialysis requirement and number of organ systems involved.
Results: 70 patients with diabetes mellitus and acute renal failure were studied. Most common causes of acute renal failure were found to be sepsis and urinary tract obstruction. Most common cause of urinary tract obstruction was papillary necrosis. NSAID was most common cause of drug induced renal failure. Out of total 17 patients who underwent renal biopsy, 9 received steroid treatments had AIN, 1 had diffuse proliferative glomerulonephritis (DPGN). Out of 9 patients who had received steroid treatment, 6 patients had recovery of renal failure. Recovery of acute renal failure was found in 64.3% of the study group. Patients with urinary tract obstruction seemed to have better outcome of ARF recovery, when compared with other causes of acute renal failure, though it did not reach statistical significance.
Duration of renal failure >10 days seemed to have poor outcome of ARF recovery, though it did not reach statistical significance. Surprisingly patients with sepsis appeared to have better outcome of ARF recovery, compared to other causes of renal failure with statistical significance.
Conclusions: Most common causes of renal failure in our study were found to be sepsis and urinary tract obstruction. Acute renal failure recovered in 64.3%. Patients with urinary tract obstruction and sepsis seemed to have favorable outcome in ARF recovery.