Helmut G. Rennke

Bio: Helmut G. Rennke is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Renal function & Kidney. The author has an hindex of 77, co-authored 256 publications receiving 33959 citations. Previous affiliations of Helmut G. Rennke include Boston Medical Center & Mayo Clinic.

Hyperfiltration in remnant nephrons : A potentially adverse response to renal ablation

Abstract: Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.

Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension.

Abstract: Two groups of adult male Munich-Wistar rats and a third group of nondiabetic age-matched and weight-matched normal control rats underwent micropuncture study 1 mo, and morphologic studies 14 mo, after induction of streptozotocin diabetes or sham treatment. All animals were fed standard rat chow. Diabetic rats received daily ultralente insulin to maintain stable moderate hyperglycemia (approximately 350 mg/dl). In addition, one group of diabetic rats was treated with the angiotensin I converting enzyme inhibitor, enalapril, 15 mg/liter of drinking water. Average kidney weight, whole kidney and single-nephron glomerular filtration rate, and glomerular plasma flow rate were elevated to similar values in both groups of diabetic rats, relative to normal control rats. Non-enalapril-treated diabetic rats exhibited significant elevations in mean glomerular capillary hydraulic pressure and transcapillary hydraulic pressure gradient, compared with the other groups studied, and only this group eventually developed marked and progressive albuminuria. Likewise, histological examination of the kidneys at 14 mo disclosed a high incidence of glomerular structural abnormalities only in non-enalapril-treated diabetic rats. These findings indicate that prevention of glomerular capillary hypertension in rats with diabetes mellitus effectively protects against the subsequent development of glomerular structural injury and proteinuria. This protection is afforded despite pronounced hyperglycemia and elevated levels of glucosylated hemoglobin, further supporting our view that hemodynamic rather than metabolic factors predominate in the pathogenesis of diabetic glomerulopathy.

Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.

Abstract: Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition FSGS is characterized by increased urinary protein excretion and decreasing kidney function Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4 Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage

Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat.

Abstract: Micropuncture and morphologic studies were performed in six groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 4 received no specific therapy. Groups 2 and 5 were treated with the angiotensin I-converting enzyme inhibitor, enalapril, 50 mg/liter, in the drinking water. Groups 3 and 6 were treated with reserpine (5 mg/liter), hydralazine (80 mg/liter), and hydrochlorothiazide (25 mg/liter). All rats were fed standard chow. Groups 1-3 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure gradient (delta P) and glomerular plasma flow rate (QA). In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained delta P at near-normal levels without significant reduction in SNGFR and QA. In contrast, triple drug therapy normalized systemic hypertension, but failed to lower delta P in group 3 rats. Groups 4-6 were followed for 12 wk after renal ablation. Untreated group 4 rats demonstrated continuous systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and frequent areas of segmental sclerosis. In group 5 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 12-wk period and dramatically limited the development of proteinuria and glomerular lesions. Despite equivalent systemic blood pressure control in group 6 rats, failure of triple drug therapy to control glomerular hypertension was associated with progressive proteinuria and glomerular lesions comparable to those seen in untreated group 4 rats. Thus, unless glomerular capillary hypertension is corrected, control of systemic blood pressure is insufficient to prevent progressive renal injury in rats with reduced renal mass.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

A New Equation to Estimate Glomerular Filtration Rate

Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...

Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

Abstract: Background End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. Methods We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. Results The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1....

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

Abstract: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net ) Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes

Abstract: Background It is unknown whether either the angiotensin-II–receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. Methods We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. Results The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo gro...