Atherosclerotic renovascular disease and progressive renal failure.

PURPOSE: To evaluate information on the prevalence and rate of progression of atherosclerotic renovascular disease and the effect of angiotensin-converting enzyme inhibition on this process, with the goal of developing a rational approach to the diagnosis and management of this disorder. DATA SOURCES: Relevant articles were identified from the authors' files and from MEDLINE searches. Additional references were obtained from the bibliographies of identified articles. STUDY SELECTION: Virtually no controlled prospective studies have been reported. The articles presented are primarily retrospective analyses and include those that provide sufficient information about the incidence or progression of renovascular disease and about the outcome and mortality rate associated with various treatments, to allow evaluation. DATA EXTRACTION: For the outcomes of interest, data from individual reports are presented in tabular form, the results summed, and averages obtained. RESULTS: Atherosclerotic renovascular disease, in many cases involving both renal arteries, is a common finding in patients older than 50 years, particularly those with diffuse atherosclerotic vascular disease. Hypertension is not a particularly sensitive indicator of this disease (almost one half are not hypertensive). The disease progresses and may account for 5% to 15% of all patients developing end-stage renal disease each year. Angiotensin-converting enzyme inhibition may damage ischemic renal tissue, but this is counterbalanced by beneficial effects of this therapy. Once end-stage renal disease is present, mortality rates are high despite dialysis support (> 50% over 3 years). Both surgery and angioplasty can preserve or improve renal function and may delay or prevent the need for dialysis therapy. These invasive procedures may have lower rates of morbidity and mortality than the so-called "conservative" approach of dialysis therapy when renal failure develops. CONCLUSIONS: Given available information, diagnosis and intervention should be considered seriously in patients at high risk for renovascular disease who have clearly progressing renal insufficiency. Prospective trials are needed, however, to determine the costs and benefits of each approach to treatment in all patients with renovascular disease and renal insufficiency.

Histone-DNA interactions and their modulation by phosphorylation of -Ser-Pro-X-Lys/Arg- motifs.

The sea urchin sperm-specific histones H1 and H2B are multiply phosphorylated in spermatids, dephosphorylated in the final stages of spermatogenesis to give mature sperm, and rephosphorylated upon fertilization. Phosphorylation in spermatids, and probably at fertilization, occurs at repeated -Ser-Pro-X-Basic-motifs in the distinctive N-terminal basic domains of both histones and at the end of the much longer C-terminal domain of H1. Here we identify the consequences of multiple phosphorylation through comparison of some physical and biochemical properties of spermatid (phosphorylated) and sperm (dephosphorylated) chromatin and histones. Study of the DNA binding properties of the intact histones and isolated basic domains suggests that phosphorylation at three dispersed sites in the C-terminal tail of H1 has little effect on its overall DNA binding affinity, whereas, strikingly, binding of the N-terminal domains of H2B and H1 is abolished by phosphorylation at four or six tandemly repeated sites respectively. Together with the relative timing of events in vivo, this suggests that phosphorylation/dephosphorylation of the N-terminal (and distal end of the C-terminal) tail of H1, and/or the N-terminal tail of H2B, effectively controls intermolecular interactions between adjacent chromatin filaments, and hence chromatin packing in the sperm nucleus.

Focal segmental glomerulosclerosis in patients receiving lithium carbonate.

Lithium carbonate is a commonly used psychiatric medication with a number of toxic renal effects, which include nephrotic-range proteinuria. A review of the literature concerning lithium-induced proteinuria is presented and three cases of nephrotic-range proteinuria are described in association with lithium therapy. The pathology in these three cases was focal segmental glomerulosclerosis, a finding not previously described.

Hyperkalemia as a complication of drug therapy.

A wide array of drugs in common use can produce hyperkalemia. We reviewed our experience with severe hyperkalemia (potassium levels greater than 5.9 mEq/L [greater than 5.9 mmol/L]) in adult inpatients during a one-year period, to evaluate the extent to which drugs could be implicated in this electrolyte disorder. Excluding hemolyzed samples, single unexplained values, and measurements obtained during cardiopulmonary bypass or resuscitation, drug therapy was a probable contributing factor in more than 60% of the hyperkalemic episodes; in 25%, drugs were temporally linked to the onset of the hyperkalemia. In declining order of frequency, the drugs associated with hyperkalemia were potassium chloride, captopril, nonsteroidal anti-inflammatory agents, and potassium-sparing diuretics. In more than 80% of the drug-related hyperkalemic episodes, potassium regulation was compromised by underlying disease states. The most common was renal insufficiency, followed by diabetes mellitus and metabolic acidosis. This review underscores the dictum that caution should be exercised when drugs with hyperkalemic potential are used in patients with impaired potassium homeostasis.

Renal transplantation in diabetes mellitus. Influence of preexisting vascular disease on outcome.

We reviewed the recommendations and outcomes for all patients with diabetes mellitus and end-stage renal disease referred to the Medical Center Hospital of Vermont from 1971 through December 1983. During this period, we recommended transplantation in 53 of 73 patients evaluated. Thirty-two transplants were performed in 30 patients. Of the 30 patients, 10 had clinical vascular disease prior to transplantation, i.e., claudication, amputation, active angina, myocardial infarction, or stroke. Seven of the 10 had only claudication or amputation. These 10 patients showed a clear excess in graft failure and mortality. One- and 2-year graft survival was 37 and 13%; patient survival was 48 and 24%. By comparison, the 20 patients without evident vascular disease had 1- and 2-year graft survival rates of 83 and 75% and patient survival rates of 85% at both 1 and 2 years. The incidence of cardiovascular death in the group with vascular disease was 45% at 1 year and 63% at 2 years, as compared with none in the group without vascular disease. The high graft loss and mortality in this group after transplantation should be a major consideration when therapeutic alternatives are considered in diabetics with end-stage renal disease.