Epidermal growth factor inhibits the hydroosmotic effect of vasopressin in the isolated perfused rabbit cortical collecting tubule.

Epidermal growth factor (EGF) is a 53-amino acid polypeptide which is a potent mitogen for cultured cells. The kidney has recently been shown to be a major site of synthesis for the EGF precursor. EGF infusions in sheep result in a diuresis and natriuresis despite a fall in GFR, suggesting a direct tubular effect. Using in vitro microperfusion of rabbit cortical collecting tubules (CCTs) at 37 degrees C, we examined the effect of EGF on the transepithelial voltage (Vt) and arginine vasopressin (AVP)-stimulated hydraulic conductivity (Lp). Pretreatment with peritubular EGF at concentrations from 10(-8) to 10(-12) M resulted in a 50% inhibition of both AVP- and 8-chlorophenythio-cyclic AMP-stimulated peak Lp. This effect was reversed by the protein kinase C inhibitor, staurosporine, but unaffected by indomethacin. CCTs with an initially negative Vt, depolarized after exposure to bath EGF. 10(-8) M EGF applied from the lumen had no effect on either Lp or Vt. Specific binding of 20 nM 125I-EGF to microdissected CCTs was also demonstrated. These results suggest that EGF can modulate both salt and water transport in the CCT via a receptor linked to protein kinase C activation.

Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group.

African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m2 were randomly assigned to a usual or low mean arterial pressure (MAP) goal of < or = 107 or < or = 92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (+/-SE) GFR decline over 3 years in the low blood pressure group was 11.8+/-7.3 mL/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3+/-1.3 mL/min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP < or = 92 mm Hg) in black and white patients with proteinuria (> 1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.

Therapeutic interventions for nephropathy in type I diabetes mellitus.

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and shown to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. Studies have shown that in patients with insulin-dependent diabetes and proteinuria, lowering systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death independent of their effect on systemic blood pressure. In studies with small numbers of patients, dietary protein restriction has also been shown to slow the rate of decline of renal function. New potential interventions currently undergoing study include treatment with aldose reductase inhibitors, treatment with inhibitors of the formation of advanced glycosylation end-products, treatment of dyslipidemia, and a variety of other less well-studied interventions.

The natural history of renal artery stenosis: who should be evaluated for suspected ischemic nephropathy?

Ischemic renal disease is defined as a clinically significant reduction in glomerular filtration rate in patients with hemodynamically significant renal artery stenosis. The most common etiology for this is atherosclerotic renal artery disease. The three major clinical settings in which one must suspect ischemic renal disease include acute renal failure precipitated by the treatment of hypertension particularly with angiotensin-converting enzyme inhibitors; progressive azotemia in a patient with known renal vascular hypertension treated medically; and unexplained progressive azotemia in an elderly patient with refractory hypertension and other evidence of atherosclerotic disease. Prevalence of ischemic renal disease secondary to atherosclerosis can be estimated from the incidence of atherosclerotic renal artery lesions leading to renal vascular hypertension and the natural history of these lesions. Autopsy series, arteriography studies, and review of populations of patients in end-stage renal disease programs all suggest that ischemic renal disease has a high and increasing prevalence in our aging population.

Elemental mercury vapour toxicity, treatment, and prognosis after acute, intensive exposure in chloralkali plant workers. Part II: Hyperchloraemia and genitourinary symptoms.

Exposure to elemental mercury vapour is known to influence renal function; however, severe renal disease has not been consistently identified. Eleven men were evaluated for renal disease after acute, massive mercury poisoning. Significant hyperchloraemia was identified in this group of patient and a reversible renal tubular defect was suggested by low normal serum bicarbonate, a normal serum anion gap and a positive urinary anion gap. The only other evidence of renal dysfunction was transient, mild proteinuria in one of the 11 patients. During this same time period, neuropsychological impairment was identified on a test of cognitive and visual-motor function, 'Trailmaking B', in seven of the 11 patients. Additionally, dysuria and ejaculatory pain occurred without evidence of urological disease. These complaints were more frequent in those patients with impairment on 'Trailmaking B' suggesting a neurological basis for these symptoms. The findings of this study support earlier observations that the brain rather than the kidney is the critical target organ after elemental mercury vapour exposure.

Diabetic nephropathy in insulin-dependent patients.

Diabetic nephropathy is a serious complication of insulin-dependent diabetes mellitus (IDDM) that affects 30% to 40% of IDDM patients with a predictable time of onset. Epidemiologic data suggest that either a genetic susceptibility, perhaps for hypertension (HTN), or an environmental exposure selects out that subset of IDDM patients and destines them to develop diabetic nephropathy. Hopefully, assessing glomerular hyperfiltration, urinary albumin excretion rate (AER), glycemic control, mean arterial pressure (MAP), and perhaps early morphologic changes will allow early identification of this high-risk group of IDDM patients before overt nephropathy is present. Once nephropathy appears, renal function inexorably declines, although the natural history of this progression may be changing with earlier therapeutic intervention. IDDM patients with nephropathy suffer a high mortality rate compared with IDDM patients without nephropathy or with nondiabetic end-stage renal disease patients. This is primarily due to malignant atherosclerotic disease manifested as coronary, peripheral, and cerebral arterial disease. Therapeutic interventions of demonstrated benefit in slowing the rate of decline of glomerular filtration rate (GFR) include blood pressure control and low-protein diets. Strict blood sugar control or treatment with aldose reductase inhibitors, converting enzyme inhibitors (CEIs), or inhibitors of advanced glycosylation end-product formation are of possible benefit, but are awaiting clinical trial results.

Medical management of nephropathy in type I diabetes mellitus: current recommendations.

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and demonstrated to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. The Diabetes Control and Complications Trial demonstrated that microalbuminuria developed in fewer patients in the intensive blood sugar control group than in the conventional therapy group. Similarly, the risk of developing proteinuria was reduced by intensive blood sugar control. Multiple studies have demonstrated that in patients with insulin-dependent diabetes and proteinuria, lowering the systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of ACE inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death. In studies in small numbers of patients with insulin-dependent diabetes and established diabetic nephropathy, dietary protein restriction has also been demonstrated to slow the rate of decline of renal function. New potential interventions currently undergoing study include the use of aldose reductase inhibitors, the use of drugs that prevent the formation of advanced glycosylation end-products, and the use of angiotensin II receptor antagonists. Thus, several established benefits have recently been demonstrated to help prevent the development of or slow the progression of diabetic nephropathy, including blood pressure control, blood sugar control, and treatment with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple new interventions are undergoing clinical trials currently.

Atherosclerotic ischemic renal disease.

Over the past decade, ischemic nephropathy has gained recognition as a distinct and treatable clinical entity. Atherosclerotic renal artery stenosis is the leading cause of ischemic renal disease. Among the aging population entering renal replacement programs, both renal artery and systemic atherosclerosis are common. Over recent years, patients with ischemic renal disease are presenting later and have diffuse atherosclerosis and other comorbid conditions. Improved screening techniques, patient selection, and interventional approaches have resulted in better outcomes in most centers. Percutaneous transluminal renal angioplasty has emerged as the treatment of choice in some centers for nonostial renal artery stenosis. Both percutaneous transluminal renal angioplasty and surgical repair have proven beneficial for renal function salvage. Many studies have elegantly demonstrated the pathophysiologic consequences of acute ischemia to the kidney. The concepts derived from acute studies have served as a springboard for considering the adaptive and maladaptive renal responses to chronic ischemia.

Serum albumin: a predictor of long-term outcome in peritoneal dialysis patients.

We report a long-term follow-up of 71 peritoneal dialysis patients who participated in a prior study that evaluated the serum albumin concentration as a predictor of short-term morbidity. In this study the use of the original serum albumin level to predict failure of peritoneal dialysis or death was investigated. Sixty-nine of the original 71 study patients were followed for 2 years from the time of enrollment in the initial study. Patients who died within this 2-year period had a significantly lower serum albumin concentration during the original study period (2.7 +/- 0.7; n = 8) than those remaining on peritoneal dialysis (3.6 +/- 0.4, n = 31), those transferred to hemodialysis (3.4 +/- 0.5; n = 13), or those receiving renal transplants (3.6 +/- 0.4 g/dL; n = 17) (P < 0.05 for all comparisons v the group that died). A low serum albumin during the original study period was not predictive of patients who transferred to hemodialysis. We conclude that the stable outpatient serum albumin concentration in peritoneal dialysis patients is a powerful predictor of mortality as well as of short-term morbidity.

The epidermal growth factor precursor isolated from murine kidney membranes. Chemical characterization and biological properties.

To understand the biology and the biochemistry of the epidermal growth factor (EGF) precursor in normal tissues we partially purified the EGF precursor from mouse kidney. The precursor was purified by affinity chromatography, using wheat germ lectin and antibodies to murine EGF. The EGF precursor is a glycosylated integral membrane protein of apparent molecular mass of 140-150 kDa. The solubilized EGF precursor is biologically active as evidenced by its ability to compete with 125I-labeled EGF for binding to the EGF receptor in intact fibroblasts and its ability to stimulate the growth of cells dependent on EGF for growth. The EGF precursor from mouse kidney can be proteolytically processed by the EGF-associated arginine esterase into a smaller fragment (97 kDa) that retains both immunologic sensitivity to EGF antiserum and biological activity. Extensive digestion of the EGF precursor with pepsin liberates a biologically and immunologically active protein of approximately the size of mature EGF.

Nontuberculous mycobacterial peritonitis during continuous ambulatory peritoneal dialysis: case report and review of diagnostic and therapeutic strategies.

Nontuberculous mycobacteria (NTM) are responsible for an increasing proportion of mycobacterial disease. Peritonitis due to NTM is an unusual but treatable complication of continuous ambulatory peritoneal dialysis (CAPD). Its presentation is similar to that of typical bacterial peritonitis, but special culture techniques are required to avoid a delay in diagnosis. Successful treatment depends on early catheter removal, drainage of fluid collections, and appropriate use of antimicrobial agents. We report a case of Mycobacterium fortuitum peritonitis in a patient undergoing CAPD, and review all previously reported cases. Diagnostic and therapeutic strategies are summarized based on available literature.

Cholesterol as a predictor of progression in nondiabetic chronic renal disease.

In summary, then, there is an accumulating body of clinical human data supporting the concept that lipid nephrotoxicity may be important in the initiation of renal injury, and that lipids play a synergistic role in the inexorable process of progression to end-stage renal disease in nondiabetic as well as diabetic chronic renal disease. Further clarification of the role of lipid nephrotoxicity and impact of therapeutic interventions await data from larger prospective studies aimed at this specific question.

Isolation of human immunodeficiency virus from peritoneal dialysate.

Human immunodeficiency virus (HIV)-seropositive individuals represent a growing population of peritoneal dialysis (PD) patients. An important health care issue in these patients is the potential for their PD fluid to transmit virus. Some body fluids, such as urine, have been demonstrated to be negative for HIV and therefore presumably to be of low risk for virus transmission. To determine whether HIV could be recovered from PD fluid, we cultured the PD fluid from two asymptomatic HIV-seropositive patients and one patient with the acquired immunodeficiency syndrome (AIDS). HIV was isolated from both the PD fluid and the blood of two of the three patients tested, one being only HIV-seropositive and one with AIDS. These findings indicate that such fluid could potentially be a source of viral transmission and emphasize the need for conscientious application of universal precautions both in and out of the hospital.

Ischemic nephropathy.

Data suggest that ischemic renal disease secondary to atherosclerotic renal artery stenosis is a prevalent health problem. Atherosclerotic renal artery stenosis is a rapidly progressive process that can result in end-stage renal disease. Renal arteriography is the current diagnostic method of choice for the demonstration of renal artery stenosis. Captopril renography, nuclear magnetic resonance angiography, and duplex scanning are promising screening tests for this disorder. Therapeutic options include medical management, percutaneous angioplasty, and surgical revascularization.

Segmental distribution of epidermal growth factor binding sites in rabbit nephron.

The kidney possesses epidermal growth factor (EGF) receptors and is a major site of synthesis for the EGF precursor, prepro-EGF. To examine the segmental localization of EGF receptors in the rabbit kidney, we characterized 125I-labeled EGF binding to micro-dissected rabbit nephron segments. Specific binding constituted 70-80% of total binding and was saturable with an apparent Kd of 8 nM. Kinetic studies (0 degrees C) revealed an association t1/2 of 20.7 min and a dissociation t1/2 of 27 min. Competition studies revealed that 125I-EGF binding was inhibited by unlabeled EGF or its homologue transforming growth factor-alpha, but not by parathyroid hormone or insulin. Mapping studies showed specific 125I-EGF binding (attomoles per centimeter) was highest in proximal straight tubules, followed by proximal convoluted tubules, cortical collecting ducts, inner medullary collecting ducts, outer medullary collecting ducts, and distal convoluted tubules. Specific binding to glomeruli was also observed. Interestingly, no specific binding of 125I-EGF to thick ascending limbs, a site of EGF precursor synthesis, was observed. These studies suggest potential sites of action for EGF in the rabbit kidney.

Macroscopic hematuria secondary to hypercalciuria and hyperuricosuria.

An adult presenting with asymptomatic gross hematuria attributable to hypercalciuria and hyperuricosuria is described. Extensive evaluations for other causes of hematuria were negative, and the gross hematuria resolved with treatment of the hypercalciuria and hyperuricosuria. Hematuria commonly attributable to these metabolic causes in children may also occur in adults. A 24-hour urine collection for the measurement of calcium and uric acid excretion in adults without nephrolithiasis may play an important role in the evaluation of hematuria.

Page kidney: case report and review of the literature.

Page kidney is caused by the accumulation of blood in the perinephric or subcapsular space, resulting in compression of the involved kidney, renal ischemia, and high renin hypertension. Most patients are young hypertensives with a remote history of blunt trauma to the abdomen or back. We describe a case of acute Page kidney following a renal biopsy in a patient with underlying IgA nephropathy. In addition to the new-onset hypertension, this patient developed a significant decline in renal function due to the inability of the contralateral diseased kidney to compensate. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were valuable in making this diagnosis. Medical and surgical therapeutic options were considered. This report also reviews all previously described cases of Page kidney.