Diagnosing vascular causes of renal failure.

The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.

Cutaneous oxalosis after long-term hemodialysis.

A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

Serum creatinine concentration at the onset of uremia: higher levels in black males.

We compared serum creatinine and blood urea nitrogen concentrations, estimated creatinine clearances and frequency of uremic symptoms at the start of chronic hemodialysis in all 20 black and 179 white males treated between 1969 and 1983. Serum creatinine concentrations were significantly higher in black males (16.5 +/- 5.9 mg/dl) than in white males (11.7 +/- 4.7 mg/dl; p = 0.016). There were no significant differences in blood urea nitrogen concentration, estimated creatinine clearance and frequency of uremic symptoms between the two groups. Blood urea nitrogen to serum creatinine ratios were lower in black males, (7.3 +/- 1.9) than in white males (11.4 +/- 3.8; p = 0.0001), and only one black male had a ratio greater than 10 compared to 60% of whites. We concluded that black males tend to have higher serum creatinine concentrations than white males at the onset of uremic symptoms, and that higher striated muscle creatinine production in black males and not lower renal function may be the cause.

Complete recovery after massive ethylene glycol ingestion.

We treated a 64-year-old man who recovered completely from a massive antifreeze ingestion with ethylene glycol levels well above those of previously described survivors. Rapid and aggressive treatment of the patient with recognized methods, including hemodialysis, resulted in the favorable outcome.

The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings.

Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis.

Oral estrogens decrease bleeding time and improve clinical bleeding in patients with renal failure.

PURPOSE: A prolonged bleeding time is associated with platelet dysfunction and clinical bleeding in patients with renal failure. Parenteral estrogens have been shown to shorten the prolonged bleeding time in patients with chronic renal failure, although the mechanism of action is unknown. We conducted a study to evaluate the efficacy of oral conjugated estrogens in this setting. PATIENTS AND METHODS: Four patients with renal failure, prolonged bleeding time, and clinical bleeding were given 50 mg of conjugated estrogen (Premarin) daily. RESULTS: Bleeding time normalized in two cases and was reduced to less than 50% of the pretreatment value in one of the remaining two cases. Bleeding stopped in all patients within two days. Ten dialysis patients with prolonged bleeding time were randomized to a course of 50 mg of Premarin daily or placebo. The bleeding time in all five patients in the Premarin group normalized or decreased to below 50% of the pretreatment value after 7.0 +/- 4.2 days of therapy. The bleeding time did not normalize in the five patients treated with placebo. No side effects attributable to therapy were reported. CONCLUSION: We conclude that orally administered conjugated estrogens effectively improve the bleeding tendency in patients with chronic renal failure.

Acute renal insufficiency due to renal infarctions in a patient with neurofibromatosis.

Manifestations of neurofibromatosis in the skin, the eye, and the skeletal and nervous systems have been well documented since the disease was first described in 1882. Stenosing vascular lesions as complications of neurofibromatosis were first reported in 1945. They are being increasingly recognized and most commonly involve the renal artery. Renal artery stenosis (usually proximal), intraparenchymal renal arterial abnormalities, and coarctation of the abdominal aorta often lead to hypertension. However, despite reports of bilateral and severe renal artery disease, renal infarction and resulting renal insufficiency have not been described. We present the case of a 35-year-old woman with neurofibromatosis and chronic hypertension associated with narrowing of right intrarenal arteries. The patient had two separate episodes of left renal infarction documented clinically and radiographically. The second infarct resulted in renal insufficieny. There was no hypercoagulopathy or source for embolism. This case suggests that renal infarction and renal insufficiency are additional complications of neurofibromatosis.

Renal failure caused by chemicals, foods, plants, animal venoms, and misuse of drugs. An overview.

Nephrotoxicity caused by contrast media and drugs is a frequent cause of renal failure in medical practice. However, there are only sporadic cases of renal failure caused by chemicals, foods, plants, animal venoms, and misused or illegal drugs, and standard medical textbooks are limited in the coverage given to the subject. This review provides a referenced compilation of these lesser-known nephrotoxins and gives an overview of renal failure caused by substances other than properly used medications.

Plasma aluminum levels (unstimulated and stimulated): clinical and biochemical findings in 185 patients undergoing chronic hemodialysis for 4 to 95 months.

Plasma aluminum levels (unstimulated and stimulated by deferoxamine infusion), along with signs and symptoms associated with aluminum overload, were evaluated in 185 patients (97 men, 88 women; mean age, 58 +/- 8 years) who had been undergoing dialysis for 4 to 95 months and who were still receiving treatment in 1985 at a free-standing dialysis facility which has always used water purified by reverse osmosis. Monthly water aluminum levels never exceeded 15 micrograms/L; therefore, the major source of aluminum in these patients was oral phosphate binders. Unstimulated plasma aluminum levels ranged from 7 to 392 micrograms/L, averaged 81.5 +/- 56.4, and did not correlate with the duration of dialysis (r = 0.07; P greater than 0.31) or frequency of symptoms. Stimulated plasma aluminum levels increased in a linear fashion (r = 0.57; P less than 0.0001) with time on dialysis; however, there was no statistical association between the stimulated aluminum levels and a variety of nonspecific musculoskeletal or CNS symptoms, evidence of hyperparathyroidism, hematocrit, or calcium or phosphorus levels. These findings suggest that total body aluminum, as reflected in deferoxamine-stimulated serum aluminum levels, increases as a function of time undergoing dialysis.

Clinical and laboratory features of patients with chronic renal disease at the start of dialysis.

We examined clinical and laboratory features retrospectively in 402 patients at the start of chronic hemodialysis in order to define better the "uremic syndrome" in the dialysis era. The information gathered included demographic data, renal diagnoses, uremic symptoms, biochemical values, and prevalences of hypertension (69%), diabetes mellitus (23%) and ischemic heart disease (16%). Unexpected findings were the wide ranges of serum creatinine levels (3.5 to 35 mg/dl) and blood urea nitrogen levels (35 to 345 mg/dl), and the frequency of hyponatremia (27%), hypoalbuminemia (52%), and anion gaps above 25 mg/dl (5%). There were higher hematocrits in males and diabetics, lower serum creatinine levels in females, diabetics and older patients, and lower blood urea nitrogen levels in blacks. The time interval from diagnosis of diabetes mellitus to initiation of dialysis in patients with diabetic nephropathy due to juvenile-onset diabetes mellitus (20.6 +/- 6.8 years) was twice that in adult onset diabetes mellitus (10.3 +/- 8.3 years).

Infants of azotemic mothers: a report of three live births.

Women with severe renal failure rarely conceive, and when they do become pregnant these women often deliver prematurely. The clinical course of mothers with renal failure has been described, but little attention has been given to the offspring. In this report, we provide data on three infants born prematurely to mothers either on dialysis or with severe renal failure. The infants were the appropriate size for gestational age and demonstrated no obvious physical abnormalities. Laboratory data, including renal function, was also within normal limits. Renal size in the two infants studied by ultrasound was near or above the 95th percentile when corrected for gestational age. The premature birth appeared to be a function of maternal complications rather than a primary in utero growth disturbance.

Circulating heavy IgM in IgM nephropathy.

IgM nephropathy (IgMN) causes nephrotic syndrome and is characterized by IgM mesangial deposits. It is speculated that these deposits are derived from circulating IgM aggregates or immune complexes, either of which would have a molecular weight heavier than that of normal IgM. To test this hypothesis the sera of 11 patients with IgMN, five patients with nephrotic syndrome of other etiologies, and 13 normal controls were analysed for such heavy IgM. The serum samples were passed over a Biogel A5M molecular sieve column and the fractions were tested for IgM concentration by enzyme linked immunosorbent assay (ELISA). The column effluent from the void volume to the IgM peak was divided into four equal regions, and the average IgM concentrations in each region were compared. The IgMN group had significantly higher IgM concentrations than normal controls in the heaviest region (0.81 +/- 0.84 vs. 0.32 +/- 0.17 micrograms/ml; P = 0.01) and in the lightest region (95.8 +/- 59.5 vs. 46.3 +/- 41.2 micrograms/ml; P = 0.02). Although the IgMN group appeared to have about double the IgM levels of the nephrotic control group in all four regions, this was only significant in the lightest (19S) region. In serum samples from two IgMN patient methods known to break antigen antibody bonds eliminated the heavy IgM; in one case we used gel filtration in potassium thiocyanate and in another ultracentrifugation at pH 2.8. In addition, the heavy IgM in this second patient exhibited complement fixation activity in a sandwich ELISA for IgM-C3 complexes. We conclude that IgMN patients have circulating heavy IgM, which by preliminary studies probably consists of complement fixing IgM immune complexes.

Increased body aluminum. An independent risk factor in patients undergoing long-term hemodialysis?

The clinical course and aluminum status of 38 patients who had been receiving dialysis for at least eight years and were still undergoing dialysis in 1985 were evaluated. Twenty-nine had evidence of increased aluminum burden, although only three had evidence of overt aluminum toxicity, and nine did not have evidence of increased aluminum burden. The patients in both the high- and low-aluminum group were similar with regard to age, the cause of their renal failure, presence of hypertension or coronary artery disease, previous parathyroidectomy, and a number of biochemical parameters, along with the amount of prescribed aluminum. All patients were followed up for the next two years or until they died. The amount of ingested aluminum was reduced, and in selected patients, treatment with intermittent infusions of deferoxamine mesylate was instituted. There were no deaths in the low-aluminum group, but ten of 29 died in the high-aluminum group: seven of vascular disease and three of infection. In addition, morbidity as defined by hospitalization for coronary or cerebral vascular disease or infection occurred in only two of the nine patients in the low-aluminum group and in 19 of the 29 patients in the high-aluminum group. These observations imply that the occurrence of increased body aluminum, as suggested by aluminum blood levels or by results of bone biopsies in some patients, has an adverse effect on morbidity and mortality and should be considered as a possible independent risk factor in patients who are receiving long-term hemodialysis.

Severe glomerulonephritis with late emergence of classic Wegener's granulomatosis. Report of 4 cases and review of the literature.

We have analyzed an unusual group of 19 patients (15 previously reported) with Wegener's granulomatosis, who presented with severe glomerulonephritis and developed diagnostic respiratory lesions only after 4 to 78 months. Necrotizing glomerulonephritis, often with crescents, and rarely with vasculitis, was the predominant renal lesion. Wegener's granulomatosis was unsuspected initially, since systemic manifestations, such as fever, arthralgias, malaise, and even pulmonary hemorrhage, were nonspecific or transient, and because renal biopsy findings resembled those seen in microscopic polyarteritis or idiopathic crescentic nephritis. Despite therapy, usually with corticosteroids, only 4 patients maintained adequate renal function. Most patients were receiving chronic dialysis when respiratory involvement developed. Cavitary nodular pulmonary infiltrates were seen in 12 of the 17 patients with lung involvement, and otorhinological disease occurred in 10 patients. Arthralgias, fever, and cough, with or without hemoptysis, were common. Wegener's granulomatosis was diagnosed by lung biopsy in 15 cases and by nasal biopsy in 4. Specific treatment was required for the respiratory disease and was delayed in many patients, because of lack of awareness that Wegener's granulomatosis may present with primary glomerulonephritis and become active during chronic renal failure or dialysis. Nevertheless, all but 1 patient eventually responded to treatment, although 3 additional patients died of late complications.

Steroid-dependent nephrotic syndrome in lupus nephritis. Response to chlorambucil.

Nephrotic syndrome associated with mesangial lupus nephritis developed in a young woman. The heavy proteinuria exhibited a striking steroid-dependent course during a three-year period of time, with ten relapses occurring whenever attempts were made to withdraw prednisone therapy. A prolonged remission was induced by the administration of chlorambucil.

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.