Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

In children, steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is frequently a progressive condition resulting in end-stage renal disease. There have been no reports of effective treatment for this condition. For the past several years, the Pediatric Nephrology services at the University of California, San Diego and Stanford University Schools of Medicine have treated these patients with a protocol involving infusions of high doses of methylprednisolone, often in combination with oral alkylating agents. Twenty-three children have been treated in this manner with a follow-up of 46 +/- 5 months. Twelve of these children are in complete remission. Six have minimal to moderate proteinuria. Four children remain nephrotic. Each of these children has a normal glomerular filtration rate. One child developed chronic renal failure and subsequently died while on dialysis. These results appear significantly better than previous series of children with FSGS. A controlled, multi-center trial of this protocol has been proposed.

Fifty infants and children with acute renal failure were treated with acute peritoneal dialysis between 1987 and 1990. The patients were dialyzed using either a catheter introduced percutaneously over a guide-wire (n = 40) or a Tenckhoff catheter (n = 10). The cause of the acute renal failure was primary renal disease in 17 children, cardiac disease in 19, and trauma/sepsis in 14. Peritoneal dialysis succeeded in controlling metabolic abnormalities, improving fluid balance, and relieving the complications of uremia. The procedure had few major complications. Overall mortality was 50%, reflecting the serious nature of the underlying diseases. We conclude that acute peritoneal dialysis is a safe and effective treatment in most pediatric patients with acute renal failure. Our series of patients treated with acute peritoneal dialysis serves as a basis of comparison for the evaluation of new modalities of therapy in childhood acute renal failure.

Patients with prednisone-resistant nephrotic syndrome and biopsy-proven focal segmental glomerulosclerosis were treated with intravenous methylprednisone. After the first 2 weeks of therapy, the average urine protein excretion decreased from 247 to 96 mg/m²/h (p < 0.04). Two of the 7 patients have had long-term, nearly complete remissions. The other patients relapsed. One relapsing patient was retreated with methylprednisolone and is now in remission. Four relapsing patients were treated with alkylating agents, in combination with methylprednisolone. All of these patients entered complete or partial remissions. Methylprednisolone causes a significant decrease in the proteinuria of children with focal segmental glomerulosclerosis. In addition, although the follow-up period is relatively short, it would appear that methylprednisolone, often in conjunction with an alkylating agent, has significantly improved the clinical status of these patients.

We report a 14-year-old female with anaphylactoid purpura (AP) who developed pulmonary hemorrhage with acute vasculitis on lung biopsy. She improved with pulse methylprednisolone, daily prednisone and ventilatory assistance. Pulmonary vasculitis is a rare but serious manifestation of AP.