Synthesis of the pyrrole porphobilinogen by sepharose-linked -aminolevulinic acid dehydratase.

delta-Aminolevulinic acid dehydratase from Rhodopseudomonas spheroides was covalently linked to Sepharose 4B, which had been activated with cyanogen bromide. A column containing this enzyme gel readily catalyzed the synthesis of the pyrrole porphobilinogen on continuous passage of a solution of delta-aminolevulinic acid. Under the conditions of the procedures, product inhibition was minimized and a 50 to 94 percent yield was attained. A column containing about 1 milligram of enzyme was continuously operated for 27 days. Although its total activity appeared to be reduced about 30 percent at the end of this time, the bound enzyme produced approximately 200 milligrams of porphobilinogen each day, and about 5 grams of the pyrrole were isolated.

Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients. METHODS AND RESULTS: We block-randomized 50 chronic, stable hemodialysis patients on the basis of their screening predialysis tHcy levels, sex, and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d (FA group) or an equimolar amount (17 mg/d) of oral L-5-methyltetrahydrofolate (MTHF group). All 50 subjects also received 50 mg/d of oral vitamin B(6) and 1.0 mg/d of oral vitamin B(12). The mean percent reductions (+/-95% CIs) in predialysis tHcy were not significantly different: MTHF, 17.0% (12.0% to 22.0%); FA, 14.8% (9.6% to 20.1%); P=0.444 by matched ANCOVA adjusted for pretreatment tHcy. Final on-treatment values (mean with 95% CI) were MTHF, 20.0 micromol/L (18.8 to 21.2 micromol/L); FA, 19.5 micromol/L (18.3 to 20.7 micromol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients: MTHF, 2 of 25 (8%); FA, 0 of 25 (0%); Fisher's exact test of between-groups difference, P=0.490. CONCLUSIONS: Relative to high-dose folic acid, high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (ie, >90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution.

Pheochromocytoma presenting as rhabdomyolysis and acute myoglobinuric renal failure.

We report the case of a previously healthy young woman who presented with the sudden onset of rhabdomyolysis and myoglobinuric renal failure, requiring hemodialysis for 3 weeks. Common causes of rhabdomyolysis were ruled out; as renal function returned, severe hypertension was noted and a pheochromocytoma was diagnosed. We suggest that pheochromocytoma causes rhabdomyolysis and myoglobinuria via catecholamine-mediated vasoconstriction and skeletal muscle ischemia.

Lack of effect of oral N-acetylcysteine on the acute dialysis-related lowering of total plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia refractory to standard B-vitamin supplementation treatment persists in > or = 75% of maintenance dialysis patients, potentially increasing their risk for atherothrombotic sequelae. We examined whether predialysis administration of oral N-acetylcysteine (NAC), which acutely increases the non-protein bound, dialyzable fraction of plasma homocysteine, might augment the homocysteine-lowering effect of dialysis therapy. Predialysis and postdialysis total plasma homocysteine levels were determined on a control day, and on a day in which oral NAC (1200 mg) was administered predialysis in n = 11 maintenance hemodialysis patients. Although NAC treatment had no significant effect on hemodialysis removal of plasma homocysteine (P = 0.594), we observed a 16% reduction (P = 0.033) in non-fasting prehemodialysis total plasma homocysteine on the NAC treatment vs. non-treatment day. Longer term, placebo-controlled confirmation of this finding will be required to evaluate the possible chronic homocysteine-lowering efficacy of NAC treatment in hemodialysis patients.

Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study.

Hyperhomocysteinemia occurs frequently in end-stage renal disease (ESRD), but its prevalence in comparison with traditional cardiovascular disease (CVD) risk factors is unknown. Fasting total plasma homocysteine, potential determinants of plasma homocysteine (i.e., plasma B-vitamins and serine), total and HDL cholesterol, glucose, and creatinine, were determined in 24 ESRD patients on dialysis, and 24 age, gender, and race matched Framingham Offspring Study controls with normal renal function. Presence of clinical CVD and CVD risk factors was established by standardized methods. Mean plasma homocysteine was markedly higher in the ESRD patients versus controls (22.7 vs. 9.5 mumol/l). ESRD patients were 33 times more likely than controls to have hyperhomocysteinemia (> 15.8 mumol/l) (95% confidence interval, 5.7-189.6). Hyperhomocysteinemia persisted in the ESRD patients despite normal to supernormal B-vitamin status. Plasma serine levels below the tenth percentile of the control distribution were found in 75% of the ESRD patients. Oral serine supplementation caused a 37% increase in mean plasma serine, but had no effect on plasma homocysteine in four ESRD patients with supernormal plasma folate, low plasma serine, and hyperhomocysteinemia. Given its unusually high prevalence, improved management of hyperhomocysteinemia might reduce CVD sequelae in ESRD.

Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients.

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched case-control study.

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.

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.

Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients.

BACKGROUND: Mild hyperhomocysteinemia is common among maintenance hemodialysis (HD) patients and renal transplant recipients (RTR) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups. Relative to their RTR counterparts, the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens, although controlled comparison data are lacking. METHODS: We compared the relative responsiveness of (n=10) RTR and (n=39) HD patients with equivalent baseline total homocysteine (tHcy) levels (i.e., RTR range=14.2-23.6 micromol/L; HD range=14.4-24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTR received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, L-5-methyltetrahydrofolate, in addition to 50.0 mg/day of vitamin B6, and 1.0 mg/day of vitamin B12. RESULTS: The mean percent (%) reductions (+/-95% confidence interval) in tHcy were: RTR=28.1% (16.2-40.0%); HD=12.1% (6.6-17.7%), P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels. Moreover, (50.0%) of 10 of the RTR versus only (5.1%) of 39 of the HD patients had final on-treatment tHcy levels <12 micromol/L; P=0.002 for comparison of between-groups differences by Fisher's exact test. CONCLUSION: Relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate, L-5-methyltetrahydrofolate. Accordingly, RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

Treatment of hyperhomocysteinemia in end-stage renal disease.

Mild to moderate hyperhomocysteinemia (Hhcy) is observed in more than 90% of patients with end-stage renal disease (ESRD) undergoing maintenance dialysis and approximately 60% to 70% of chronic stable renal transplant recipients. The reported association between Hhcy and the development of arteriosclerotic cardiovascular disease may account, in part, for the disproportionate risk for cardiovascular morbidity and mortality in patients with chronic renal disease. Treatment with the recommended daily allowances of folic acid and vitamins B(6) and B(12), which consistently normalizes total homocysteine (tHcy) levels in the general population free of chronic renal disease, rarely results in the normalization of tHcy levels in patients with ESRD. A large number of investigations now have shown that even grossly supraphysiological doses of folic acid and vitamins B(6) and B(12) fail to normalize tHcy levels in more than 90% of dialysis-dependent patients with ESRD with baseline Hhcy. Conversely, such treatment consistently normalizes tHcy levels among hyperhomocysteinemic chronic stable renal transplant recipients or patients with mild to moderate renal insufficiency. A randomized, placebo-controlled, tHcy-lowering intervention trial involving approximately 4,000 chronic stable US renal transplant recipients (RO1 DK56486 01A2) will soon be underway to formally address the tenable hypothesis that tHcy-lowering treatment may reduce the risk for arteriosclerotic outcomes. Data from this trial should be applicable to patients with chronic renal insufficiency in general.

Residual renal function and mortality risk in hemodialysis patients.

Residual renal function, defined as the urinary clearance of urea and creatinine, is minimal in many patients treated with hemodialysis (HD) and tends to be ignored in most outcome studies involving HD patients. Recent studies showed that residual renal function, even at a low level, is influential in preventing mortality in the minority of patients with end-stage renal disease treated with peritoneal dialysis. This issue generally has not been examined in patients treated with HD. This prospective observational study of all 114 patients at a single community-based freestanding HD center is designed to examine the impact of residual renal function (defined as renal urea clearance and renal creatinine clearance derived from 24-hour urinary volumes) on mortality over a 2-year period. During that period, 50 deaths occurred in 114 patients. The presence of residual renal function was protective against mortality (odds ratio for death, 0.44; 95% confidence interval, 0.24 to 0.81; P = 0.008), even after adjustment for duration of dialysis treatment, age, smoking, presence of diabetes, presence of cardiovascular disease, serum albumin level, and urea reduction rate. In conclusion, the presence of residual renal function, even at a low level, is associated with a lower mortality risk in HD patients.

Outcome data on pediatric dialysis patients from the end-stage renal disease clinical indicators project.

Network 1 (New England) initiated the Clinical Indicator Project to survey dialysis adequacy (Kt/V), nutrition (serum albumin level), and anemia management in patients maintained on chronic dialysis. Because little information is available in children, data were specifically recorded covering these variables in patients (age, 1 to 18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD). During the 18 months of data collection, 29 observations were recorded on 23 HD patients (age, 14.3 +/- 3.6 years), and 43 observations were made on 30 PD patients (age,10.6 +/- 4.7 years). Kt/V correlated inversely with the age of the patient (HD, P < 0.004; PD, P < 0.0007). Although serum albumin level was not associated with dialysis adequacy in HD patients, there was a strong inverse relationship between albumin level and Kt/V in PD patients (P < 0.002). Hematocrit values were not significantly different in the two groups (HD, 31.0% +/- 5.5% versus PD, 32.9% +/- 4.8%) and could not be correlated with weekly erythropoietin dose. Weekly erythropoietin dose was directly related to patient age in both groups (HD, P < 0.05; PD, P < 0.02). The weekly erythropoietin dosage needed to maintain the hematocrit was greater in HD patients (HD, 11,211 +/- 7,484 U versus PD, 3,790 +/- 1,968 U; P < 0.0001). We conclude that (1) smaller children in both groups tend to have a greater Kt/V, (2) Kt/V greater than 2.75 in PD patients may not improve nutrition per se and could result in increased albumin losses, and (3) erythropoietin dosing appears to correlate best with patient size (age) rather than degree of anemia.

Effect of aminoglycoside use on residual renal function in peritoneal dialysis patients.

Residual renal function (RRF) is a major contributor to total solute clearance in peritoneal dialysis (PD) patients, and maintenance of RRF has been linked to decreased morbidity and mortality in PD. There have been few clinical studies examining the impact of factors that potentially affect RRF in PD. This is a prospective observational study that examines the effects of parenteral aminoglycosides, a common nephrotoxin in the general population, on RRF in a cohort of PD patients. Seventy-two patients from two Rhode Island PD units were observed over 4 years. Twenty-four-hour renal creatinine clearances and urine volumes were measured every 4 to 6 months. The patients were divided into three groups, depending on exposure to peritonitis and aminoglycoside use. Group I included patients without peritonitis who received no intravenous (IV) or intraperitoneal (IP) antibiotics. Group II included patients with peritonitis who received IV or IP penicillins, cephalosporins, vancomycin, or quinolones, but no aminoglycosides. Group III included patients with peritonitis who received IV or IP aminoglycosides for at least 3 days. Patients in group III had a more rapid decline in renal creatinine clearance (-0.66 +/- 0.58 mL/min/mon) than groups I and II (P < 0.005) and had a more rapid decline in daily urine volume (-74 +/- 62 mL/d/mon) than groups I and II (P < 0.01). We conclude that IV or IP aminoglycosides seem to increase the rapidity of decline in RRF in PD patients. In patients with solute clearance dependent on RRF, it seems reasonable to withhold aminoglycosides, especially if other antibiotics are available and appropriate.

Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients.

BACKGROUND: Hyperhomocysteinemia, a putative atherothrombotic risk factor, is observed in at least 85% of patients undergoing maintenance hemodialysis (HD), as well as 65 to 70% of renal transplant recipients (RTRs). The hyperhomocysteinemia regularly found in HD patients is largely refractory to combined oral vitamin B supplementation featuring supraphysiological doses of folic acid (FA). Relative to their HD counterparts, the hyperhomocysteinemia of RTRs appears to be considerably less refractory to treatment with high-dose FA-based vitamin B supplementation regimens, although controlled comparison data are lacking. We evaluated whether improved total homocysteine (tHcy)-lowering efficacy could be achieved in chronic HD patients with a high-dose L-5-methyltetrahydrofolate (MTHF)-based regimen, as suggested by recent uncontrolled findings, and compared the relative responsiveness of RTRs and HD patients with equivalent baseline tHcy levels, to 12 weeks of tHcy lowering with combined folate-based vitamin B treatment. METHODS: First, we blocked randomized 50 chronic, stable HD patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 25 subjects treated for 12 weeks with oral FA at 15 mg/day, or an equimolar amount (17 mg/day) of oral MTHF. All 50 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (+/- 95% confidence intervals) in predialysis tHcy were not significantly different [MTHF 17.0% (12.0 to 22.0%), FA 14.8% (9.6 to 20.1%), P = 0.444 by matched analysis of covariance adjusted for pretreatment tHcy]. Final on-treatment values (mean with 95% confidence interval) were: MTHF, 20.0 micromol/L (18.8 to 21.2); and FA, 19.5 micromol/L (18.3 to 20.7). Moreover, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [MTHF, 2 out of 25 (8%); FA, 0 out of 25 (0%); Fisher's exact test of between groups difference, P = 0.490]. Second, we compared the relative responsiveness of (N = 10) RTRs and (N = 39) HD patients with equivalent baseline tHcy levels (RTR range of 14.2 to 23.6 micromol/L, and HD range of 14.4 to 24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTRs received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, MTHF, in addition to 50.0 mg/day of vitamin B6 and 1.0 mg/day of vitamin B12. The mean percentage (%) reductions (+/- 95% confidence interval) in tHcy were as follows: RTR 28.1% (16.2 to 40.0%); HD 12.1% (6.6 to 17.7%, P = 0.027 for comparison of between groups differences by analysis of covariance adjusted for baseline tHcy levels). Moreover, 5 out of 10 (50.0%) of the RTR versus only 2 out of 39 (5.1%) of the HD patients had final on-treatment tHcy levels <12 micromol/L (P = 0.002 for comparison of between groups differences by Fisher's exact test). CONCLUSIONS: First, in comparison to high-dose FA, high-dose oral MTHF-based supplementation does not afford improved tHcy-lowering efficacy among HD patients. The preponderance of HD patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution. Second, relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering vitamin B treatment regimens featuring supraphysiological amounts of FA or the reduced folate MTHF. Accordingly, RTRs are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering vitamin B intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

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.

Proliferative glomerulonephritis with unusual, organized, cylindrical deposits associated with angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

We describe an elderly man who developed angioimmunoblastic lymphadenopathy-like T-cell lymphoma, followed by acute renal failure 2 months later. Renal biopsy revealed proliferative glomerulonephritis, which was characterized by enlarged glomeruli with increased cellularity, thickened capillaries, intracapillary inflammatory cells, focal necrosis, and fibrin extravasation. Immunofluorescence studies revealed capillary and mesangial deposits of IgG, IgM, IgA, Ig kappa, Ig lambda, and C3. Electron microscopy revealed unusual, organized, electron-dense deposits in the capillary walls and mesangium. The deposits occurred as accumulations of large rigid tubules or cylinders, which, in longitudinal section, were double-walled. In transverse section, the deposits were annular or horseshoe shaped and occasionally had a central filament. The morphologic characteristics of these deposits are different from those seen in cryoglobulinemia or fibrillary and immunotactoid glomerulopathies. The significance of these deposits is uncertain; they may represent a cryoglobulin or an abnormal serum protein related to angioimmunoblastic lymphadenopathy-like T-cell lymphoma. The findings in this case expand the morphologic spectrum of glomerular lesions that may be associated with malignant lymphoproliferative disorders and, particularly, angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

Renal osteodystrophy and dialysis artifacts as indicators of identification.

Evidence of rare disease may be useful in the identification of unknown remains. Osteodystrophy is a condition commonly associated with chronic renal failure. The presence of renal osteodystrophy and medical artifacts associated with the treatment of kidney failure in human remains may provide information about the individual's medical history. Currently, there are more than 100,000 patients with end stage renal disease in the United States receiving dialysis treatments to replace kidney function, and hundreds of thousands more who have significant chronic kidney failure and are not yet treated with dialysis. Chronic renal failure frequently leads to disorders in the metabolism of vitamin D, calcium, and parathyroid hormone which are extremely difficult to correct. At least three patterns of skeletal change may result: osteitis fibrosa, characterized by increased bone remodelling, increased osteoclastic activity, peritrabecular fibrosis, and a normal mineralization pattern; osteomalacia, with a markedly increased osteoid surface and volume, and impaired mineralization; and mixed osteodystrophy, with increased bone remodelling and moderately impaired mineralization. While these bone changes may not have any clinical manifestations in most patients, they can been seen radiographically and histologically. This evidence may be useful in identifying remains which have been skeletonized, burned, decomposed, or dismembered. Medical artifacts associated with dialysis treatment, such as catheters, polytetrafluoroethylene grafts, and evidence of surgical procedures, are also useful for identification.

Residual renal function in a large cohort of peritoneal dialysis patients: change over time, impact on mortality and nutrition.

OBJECTIVE: Residual renal function contributes importantly to total solute clearance in peritoneal dialysis (PD) patients. This study was designed to examine the progression of residual renal function over time and its impact on nutrition and mortality in PD patients in the six New England states (ME, NH, VT, CT, MA, RI) comprising End Stage Renal Disease (ESRD) Network 1. DESIGN: As part of the ESRD Clinical Indicators Project, data on 990 PD patients in Network 1 were abstracted from data supplied by dialysis units in the fourth quarter of 1997. This included demographic information; dose of PD in L/day; weekly renal, dialysis, and total Kt/V urea; weekly renal, dialysis, and total creatinine clearance (CCr); serum albumin level; and mortality and transplantation information. Data collection was repeated in the second and fourth quarters of 1998 and in the second quarter of 1999. PATIENTS: 990 PD patients in Network 1. OUTCOME MEASURES: The change in total and renal solute clearances over time, the relationship between renal clearance and mortality, and the relationship between renal clearance and nutritional status, as represented by serum albumin. RESULTS: Over the 2-year period, mean weekly renal Kt/V urea and weekly renal CCr dropped significantly. To examine the effect of residual renal function on mortality, patients were divided into high and low (above and below the median) weekly renal Kt/V urea and weekly renal CCr groups. Patients above the median levels of both weekly renal Kt/V urea and weekly renal CCr had a significantly decreased risk of dying during the observation period, after controlling for age, gender, serum albumin level, and diabetic status [OR for high vs low renal Kt/V urea 0.54 (CI 0.34 - 0.84), OR for high vs low renal CCr 0.61 (CI 0.40 - 0.94)]. The mean weekly renal Kt/V urea was significantly and directly correlated with the mean serum albumin level by Spearman rank correlation (R = 0.133, p < 0.001), as was the mean weekly renal CCr (R = 0.115, p < 0.001). CONCLUSIONS: Residual renal function is an important contributor to total solute clearance in PD patients. Even at low levels it is linked to decreased mortality and better nutritional status.