Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial

Membranous nephropathy is a common cause of nephrotic syndrome in adults. Although some patients with membranous nephropathy achieve a spontaneous remission, renal function continues to deteriorate in others. We conducted a prospective randomized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy. Twenty-five patients received tacrolimus (0.05 mg/kg/day) over 12 months with a 6-month taper, whereas 23 patients were in the control group. The probability of remission in the treatment group was 58, 82, and 94% after 6, 12, and 18 months but only 10, 24, and 35%, respectively in the control group. The decrease in proteinuria was significantly greater in the treatment group. Notably, six patients in the control group and only one in the treatment group reached the secondary end point of a 50% increase in their serum creatinine. No patient in the tacrolimus group showed a relapse during the taper period. Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal. We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function. The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function.     

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.     

Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria.

Angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria in diabetic and nondiabetic nephropathy. However, no studies have determined whether this antiproteinuric effect modifies the progression of renal insufficiency. We studied the evolution of 46 nondiabetic patients with nephrotic proteinuria treated with captopril for a minimum of 12 months. The follow-up period before captopril treatment was 12 to 18 months. At the end of follow-up, after captopril introduction (24.4 +/- 7.6 months), proteinuria had decreased from 6.3 +/- 2.5 to 3.9 +/- 3.1 g/24 h (P less than 0.001), with a mean decrease of 45% +/- 28%. The proteinuria decrease was higher in patients with reflux nephropathy, proteinuria associated with reduction of renal mass, inactive crescentic glomerulonephritis, nephroangiosclerosis, and IgA nephropathy, whereas patients with membranous glomerulonephritis and idiopathic focal glomerulosclerosis showed a poorer response. Patients were separated according to a proteinuria reduction greater (group A, 23 patients) or lower (group B, 23 patients) than 45% of the initial value. At the end of follow-up, renal function had not significantly changed in group A with respect to values at the start of treatment: serum creatinine (SCr) was 229 +/- 167 mumol/L (2.6 +/- 1.9 mg/dL) versus 203 +/- 97 mumol/L (2.3 +/- 1.1 mg/dL), and creatinine clearance (CrCl) was 0.80 +/- 0.52 mL/s (48 +/- 31 mL/min) versus 0.87 +/- 0.47 mL/s (52 +/- 28 mL/min). The slope of the reciprocal of Scr (1/SCr) showed a significantly beneficial change after captopril introduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relapsing nephrotic syndrome in a diabetic patient with minimal change

Although nondiabetic nephropathies are common among type 2 diabetic patients, very few cases of minimal change nephrotic syndrome have been reported in diabetic patients. We describe a type 2 diabetic patient that rapidly developed a nephrotic syndrome accompanied by a mild worsening of renal function. Proteinuria was negative one year before and no signs of diabetic retinopathy were found. Renal biopsy established the diagnosis of minimal change disease. Steroid treatment induced a complete remission of nephrotic syndrome and recovery of normal renal function. However, massive proteinuria relapsed two years later. A second cycle of steroids was followed by a disappearance of proteinuria, but a third bout of nephrotic syndrome was observed 6 months later. An 8-weeks cycle of steroids plus chlorambucil induced a complete and persistent remission. Throughout a five-year follow up, no relapse of the nephrotic syndrome was observed and microalbuminuria is negative.     

Partial deficit of hypoxanthine guanine phosphoribosyl transferase presenting as acute renal failure

A 12-year-old boy presented with acute renal failure (ARF) accompanied by a disproportionate increase of serum uric acid level and massive uric acid crystalluria. After alkalinization and allopurinol therapy, serum uric acid and renal function returned to normal values. A further enzymatic study showed the existence of a partial hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficit (less than 1% of HPRT normal activity). Although ARF is an exceptional form of presentation of HPRT deficiency, this possibility should be considered whenever an ARF is accompanied by disproportionate high levels of serum uric acid.