Superficial and juxtamedullary nephron function during saline loading in the dog.

A modification of the microdissection technique of Hanssen was utilized in dogs to measure superficial (SNGFR) and juxtamedullary nephron filtration rate (JMGFR) in control and saline-expanded dogs. During control studies SNGFR was 60+/-4 and JMGFR was 72+/-5 nl/min. During saline loading SNGFR was 74+/-8 and JMGFR was 65+/-6 nl/min. The ratio SNGFR: JMGFR significantly increased from 0.84+/-0.03 to 1.15+/-0.08. Glomerular perfusion rate (GPR) was measured with the microsphere method during control and saline loading. Superficial GPR did not change significantly but juxtamedullary GPR increased from 225+/-42 to 323+/-39 nl/min. Calculated superficial nephron filtration fraction was unchanged after saline expansion but juxtamedullary filtration fraction decreased from 0.34+/-0.07 to 0.24+/-0.07. The data demonstrate a tendency for filtration to shift toward the superficial part and plasma flow toward the deep part of the kidney cortex. GFR in juxtamedullary nephrons appears to be less plasma flow-dependent than in superficial nephrons. The fall in filtration fraction in the deep cortex may affect sodium excretion by juxtamedullary nephrons.

Restoration and maintenance of glomerular filtration by mannitol during hypoperfusion of the kidney.

Glomerular filtration (GF) during progressive reduction of renal perfusion pressure by aortic clamping was studied in hydropenic rats and in rats infused with isotonic saline, hypertonic saline, or mannitol. As judged by visual observation of Lissamine green movements in superficial nephrons. GF was absent in hydropenic or saline-loaded rats at 40 mm Hg aortic pressure, but continued in some nephrons of all rats infused with mannitol and of some rats infused with hypertonic saline. Urine flow persisted only in rats infused with mannitol. By use of the qualitative Hanssen technique, it was found that all glomeruli in superficial and deep portions of the cortex were perfused at 40 mm Hg in all groups of rats. By the same method. GF continued in 1% of nephrons in hydropenic rats, 12% of nephrons in isotonic saline-loaded rats, and 78% of nephrons in rats infused with mannitol. By means of a quantitative Hanssen technique, GF was 5.8 nl/min per nephron in mannitol-infused rats and not measurable (< 0.5 nl) in hydropenic rats. Superficial and deep nephrons were similar in both qualitative and quantitative studies. Although urine flow did not persist in rats infused with hypertonic saline, GF was detected in four of seven studies by the Hanssen method (mean, 9.1 nl/min per nephron). In additional experiments, mannitol infused after perfusion pressure had already been lowered to 40 mm Hg in hydropenic rats reestablished urine flow and GF (mean, 9.8 nl/min). Furosemide, isotonic and hypertonic saline did not restart urine flow; however, GF (Lissamine green) was restarted by hypertonic saline. We conclude that mannitol can maintain or reestablish by an extratubular mechanism GF which otherwise would not occur during renal hypoperfusion. Hypertonic saline has a similar effect on GF in some cases, but urine flow is not maintained, implying complete reabsorption of filtrate.

Effect of early plasmapheresis and immunosuppressive therapy on natural history of anti-glomerular basement membrane glomerulonephritis: report of a 22-month follow-up.

A patient with anti-glomerular basement membrane (GBM)-mediated necrotizing and proliferative glomerulonephritis with crescents was treated with plasmapheresis, cyclophosphamide, and steroids. Treatment resulted in decreased circulating anti-GBM antibody and prompt improvement of renal function that remained stable for 15 months after all treatment was discontinued. Renal biopsies were performed initially, at seven and 17 months. Immunofluorescent examination showed that anti-GBM antibody continued to be present on GBMs although light and electron microscopic findings demonstrated a transformation to a form of sclerosing glomerulonephritis. To our knowledge, this patient's course is the first demonstration that early treatment with plasmapheresis and immunosuppressions may transform the histologic findings in anti-GBM-induced rapidly progressive glomerulonephritis, thereby altering the natural history of this disease.

Rapid progressive glomerulonephritis: relapse after prolonged remission.

Three patients with epithelial cell crescents and rapid progressive glomerulonephritis (RPGN) had prolonged remission, presumably induced by treatment with maintenance oral prednisone and cyclophosphamide plus plasmapheresis. Patient 1 had anti-glomerular basement membrane-mediated RPGN, patient 2 had an immune complex disease, and patient 3 did not show any immune deposits. After a two-year remission in two patients and a greater than one-year remission in the third patient, renal function deteriorated. Epithelial cell crescents were again demonstratable on repeated renal biopsy specimens in each patient. One patient again received triple therapy, while the other two patients received megadoses of intravenous prednisolone sodium succinate in place of plasmapheresis. Each patient again entered a stable remission. These three cases demonstrate that RPGN may recur after prolonged remission in all three varieties of this syndrome. If the exacerbation is treated promptly, a second remission may be induced.

Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis.

PURPOSE: We wanted to examine the long-term effects of aggressively treating idiopathic rapidly progressive glomerulonephritis (RPGN), with a particular focus on clinically characterizing the patient population, assessing the short- and long-term effects of therapy on renal function, and determining complications of the therapy. PATIENTS AND METHODS: Twenty-three consecutive patients with RPGN were treated and followed from one to 11 years. On renal biopsy, 13 had immune complexes, eight had no immune complexes, and two had antiglomerular basement membrane deposits. All had greater than 25 percent crescents and 19 of 23 had greater than 50 percent crescents. Every patient responded on a short-term basis to either large-dose pulse methylprednisolone or plasma exchange, with reduction of the mean plasma creatinine level from 6.5 +/- 2.0 mg/dl to 2.9 +/- 1.0 mg/dl (p less than 0.001). Each patient received oral prednisone and all but one received cyclophosphamide. RESULTS: Three died of non-renal causes. Fifty percent of the remaining 20 patients maintained stable renal function for at least two years. Four of nine patients followed-up for longer than two years had a relapse, but all responded again to therapy. No characteristic clinical symptoms predicting relapse were found, although nearly all had hematuria and proteinuria. Complications of therapy were frequent and may have contributed to death in two patients. CONCLUSION: Thus, long remissions are seen in most patients with RPGN treated aggressively.

A simple comorbidity scale predicts clinical outcomes and costs in dialysis patients.

PURPOSE: In a university-based dialysis program, we found that 25% of the patients accounted for 50% of the costs and 42% of the deaths. We determined whether the Charlson Comorbidity Index, a simple measure of comorbid conditions, could predict clinical outcomes and costs in these patients. METHODS: Patients on hemodialysis or peritoneal dialysis from July 1996 to June 1998 at the University of Pittsburgh outpatient dialysis unit were studied. Comorbidity scores and outcomes were determined by reviewing the Medical Archival Retrieval System database and outpatient records. RESULTS: Two hundred sixty-eight patients were observed for 293 patient-years. The Comorbidity Index strongly predicted admission rate (relative risk per each unit increase = 1.20; 95% confidence interval [CI]: 1.16 to 1.23, P = 0.0001), hospital days and inpatient costs (both P <0.0001), and mortality (relative risk per unit increase = 1.24, 95% CI: 1.11 to 1.39, P = 0.0002.). Age and diabetes, used in the Health Care Financing Administration dialysis capitation model, correlated poorly with outcomes. CONCLUSIONS: The modified Charlson Comorbidity Index predicts outcomes and costs in dialysis patients. This index may be useful in determining appropriate payment for care of dialysis patients under capitated payment schemes and as a research tool to stratify dialysis patients in order to compare the outcomes of various interventions.

Disseminated listeriosis presenting as acute hepatitis. Case reports and review of hepatic involvement in listeriosis.

We report three cases of disseminated listeriosis that presented as acute hepatitis characterized by striking increase of liver function test values and fever. Peak serum transaminases (SGOT) for each of three patients were 5,380, 2,350, and 443 mu/ml respectively. The correct diagnosis was not suspected in any of the patients until blood and cerebrospinal fluid cultures obtained routinely in the course of evaluation for fever grew Listeria monocytogenes. When antibiotic therapy was instituted, serum transaminase values plummeted in two patients; these two were eventually cured of their infection. The third patient succumbed to his infection; postmortem examination showed miliary abscesses of the liver which revealed L. monocytogenes. Review of the literature for previous reports of hepatic involvement in adult patients with listeriosis shows that hepatitis is an unusual mode of presentation. However, since we observed these three cases over a one-year period, we suspect this may not be an uncommon occurrence.

Control of cholesterol embolization by discontinuation of anticoagulant therapy.

A 64-year-old man developed multisystem disease including renal failure while receiving anticoagulants. Renal biopsy showed cholesterol embolization. Discontinuation of anticoagulants resulted in prompt cessation of symptoms and dramatic improvement in renal function.

Effectiveness of low dose urokinase on dialysis catheter thrombolysis.

Thrombosis, a major cause of hemodialysis catheter dysfunction, can be treated with urokinase. We compared protocols using full strength urokinase to the volume of the catheter with low dose therapy. Clotting episodes and successful declottings (blood flow > 200 ml/min) were tracked for 6 months. One hundred four clotting episodes were treated with 5,000 U/ml urokinase to the volume of the catheter lumen for a 1 hr dwell. If unsuccessful, a second dose of 5,000 U/ml was administered and, if needed, a third dose of 125,000 U/lumen. Post treatment, catheters were locked with 5,000 U/ml heparin to the volume of the lumen. Using new protocols, clotting episodes were treated with 2,500 U/lumen urokinase, followed by saline to the volume of the lumen for a 1 hr dwell. A mid dwell injection of 0.2 ml/lumen saline was added to advance the front of active urokinase. If unsuccessful, a second 2,500 U/lumen dose was administered. Heparin lock was 10,000 U/ml heparin to the volume of the lumen. Revised protocols decreased clotting episodes 60% and urokinase charges 81%, while maintaining successful declottings at 74%. Low dose urokinase was as effective as full strength when the active front was advanced mid dwell.

Potentiation of uremic bleeding by hereditary storage pool disease.

This study demonstrates that specific bleeding tests can separate the thrombocytopathy of uremia alone from the bleeding disorders caused by uremia superimposed on preexisting platelet dysfunction. The case history of a uremic patient with exaggerated bleeding tendencies is presented. The findings in this patient are compared with the clinical characteristics and platelet function studies of nine other patients with chronic renal failure. The index and other uremic patients were similar except for the clinical bleeding and results of platelet function studies. The patient's nonocclusive bleeding time and measured blood loss during bleeding time tests were increased compared with the other uremic controls. In addition, her platelet aggregation in response to collagen was lower than that of the other uremic subjects. Repeat studies following renal transplantation were consistent with hereditary storage pool disease. An underlying platelet disorder may potentiate the hemostatic defects of uremia. The diagnosis should be suspected in patients with frequent and severe bleeding manifestations. Renal transplantation led to control of clinical bleeding.

Hypercalcemia in patients with advanced chronic renal failure not yet requiring dialysis.

Six patients with progressive chronic renal failure not yet requiring dialysis and not consuming supplemental calcium or vitamin D developed hypercalcemia. Three had proven and 1 suspected tertiary hyperparathyroidism, 1 parathyroid carcinoma and 1 aplastic bone. None of the 3 patients who underwent bone biopsy had heavy bone aluminum staining. The patients with proven parathyroid-mediated hypercalcemia had marked elevation of C-terminal parathyroid hormone and alkaline phosphatase values and, when performed, radiographs consistent with osteitis fibrosa. When these findings are absent or the diagnosis is otherwise uncertain, a bone biopsy may provide a definitive diagnosis and guide management.

Effect of hemodilution on the distribution of renal blood flow.

We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.

Rupture of ovarian cyst: massive hemoperitoneum in continuous ambulatory peritoneal dialysis patients: diagnosis and treatment.

Two women on continuous ambulatory peritoneal dialysis (CAPD) developed recurrent episodes of hemoperitoneum while in the reproductive age group. Initially, both were thought to have mechanical problems with the peritoneal catheter system. A laparotomy was performed in the first patient, and a bleeding ovarian cyst was identified. The second patient had ovarian cysts documented by ultrasound. Thus, abdominal pain and bloody dialysate should not just be ascribed to catheter-related problems. The second patient's midcycle bleeding was suppressed with birth control pills.

Ibuprofen-associated lipoid nephrosis without interstitial nephritis.

A report of ibuprofen-associated lipoid nephrosis without interstitial nephritis is presented. Previous reported cases had incomplete biopsy descriptions or concurrent interstitial disease. The patient responded to withdrawal of ibuprofen.

Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone.

OBJECTIVE: To determine the effect of cyclophosphamide and prednisone on progressive renal failure and on nephrotic features in patients with membranous glomerulonephritis. DESIGN: Prospective, nonrandomized time series. SETTING: Outpatient clinic at a university medical center. PATIENTS: Eleven consecutive patients with biopsy-proven membranous glomerulonephritis and rising plasma creatinine levels over at least 6 months. INTERVENTION: Cyclophosphamide and prednisone in ten patients and cyclophosphamide alone in one patient. MEASUREMENTS AND MAIN RESULTS: In ten patients treated with both agents, the median plasma creatinine rose 53 mumol/L (0.6 mg/dL) over the months before treatment from 141 to 194 mumol/L (1.6 to 2.2 mg/dL) (95% CI, 27 to 141 mumol/L; P = 0.002). After combined therapy for 6 months, the median plasma creatinine fell to 133 mumol/L (1.5 mg/dL) for a median decline of 62 mumol/L (0.7 mg/dL) (CI, 44 to 150 mumol/L; P = 0.006). Pretreatment plasma creatinine levels, which ranged from 159 to 371 mumol/L (1.8 to 4.2 mg/dL), decreased in the ten patients by 6 months and remained stable in seven of the eight patients followed 24 to 54 months after therapy was completed. The median urine protein excretion decreased by 9.6 g/d with 12 months of therapy in the ten patients from 11.9 to 2.3 g/d (CI, 6.0 to 15.1 g/d; P less than 0.001). The median plasma albumin rose by 14 g/L from 24 to 38 g/L (CI, 11 to 19 g/L; P less than 0.001). The median plasma cholesterol fell by 3.26 mumol/L (140 mg/dL) from 10.45 to 6.52 mumol/L (405 to 252 mg/dL) (CI, 1.42 to 7.16 mumol/L; P = 0.01). One patient who had a relapse 30 months after completing therapy responded to re-treatment with renal function and nephrotic variables returning toward normal. The eleventh patient received cyclophosphamide alone and had a course similar to that of the combined therapy group. CONCLUSION: Cyclophosphamide plus prednisone can promote prolonged remissions in membranous glomerulonephritis even when renal function is already declining.

Plasmapheresis as sole therapy in a patient with essential mixed cryoglobulinemia.

An 82-year-old woman with essential mixed cryoglobulinemia type II (IgM K IgG) presented with moderate renal failure and nephritic syndrome. Mesangiocapillary glomerulonephritis with mesangial and subendothelial granular deposits containing IgG, IgM, and C3 in conjunction with small-vessel vasculitis was seen on renal biopsy. Renal symptomatology preceded by a period of 10 months the development of leg ulcers and purpura. The onset of the skin lesions was accompanied by an acute decline of renal function and an increase in liver alkaline phosphatase. Plasmapheresis with a 50% plasma exchange each week over 12 weeks led to improvement in renal function, healing of leg ulcerations, disappearance of purpura, and a return to the baseline of alkaline phosphatase in association with the disappearance of circulating cryoglobulins.

Infectious complications with plasmapheresis in rapidly progressive glomerulonephritis.

We recently used plasmapheresis to treat eight patients with rapidly progressive glomerulonephritis. Life-threatening infections developed in five patients, three of which were caused by opportunistic pathogens. In contrast, only two infections occurred in 21 patients with similar renal disease treated with immunosuppressive drugs but not with plasmapheresis. Although infectious complications of plasmapheresis therapy have not been amphasized previously, our experience, coupled with that of previous reports, suggests that serious infections will develop in one third of patients undergoing plasmapheresis for renal disease. Plasmapheresis should be used with caution in patients with rapidly progressive glomerulonephritis.

Propranolol-related bronchospasm in patients without history of asthma.

Three patients with no history of asthma or allergy developed bronchospasm while taking propranolol for hypertension. The bronchospasm was severe in all three and in one patient resulted in respiratory arrest. Since the bronchospasm was relieved with discontinuation of propranolol and supportive bronchodilator therapy, the bronchospasm was believed to be caused by propranolol. Furthermore, each patient was subsequently treated with other antihypertensive medications which, like propranolol, contain the stabilizer additive tartrazine. Bronchospasm did not recur, making it unlikely that tartrazine hypersensitivity caused this problem. Regardless of a negative history of asthma, therefore, life-threatening bronchospasm must be considered a possible complication of propranolol therapy.

Evaluation of platelet hyperfunction in hemodialysis patients receiving recombinant human erythropoietin.

There are data suggesting that recombinant human erythropoietin (rHuEPO) may induce thromboses in hemodialysis patients, possibly due to alterations in platelet function. In an earlier study, we found evidence of platelet hyperfunction in several patients 4 to 8 weeks following the start of rHuEPO therapy, which was begun shortly after hemodialysis was initiated. Studies were performed to examine the effects of rHuEPO on whole blood platelet aggregation and adenosine triphosphate (ATP) release independent of changes in hematocrit or the uremic state. Eight hemodialysis patients without and four with a history of vascular access clotting had platelet aggregation tests performed at baseline while receiving rHuEPO, off rHuEPO for 2 weeks, and 4 to 6 weeks after restarting the drug. While the plasma EPO level decreased significantly after the 2-week period off rHuEPO (P < 0.0001), the hematocrit did not change at any of the three time periods. Whole blood platelet aggregation in response to adenosine diphosphate (ADP), collagen, and ristocetin was not significantly altered on or off rHuEPO in either patient group. Platelet hyperfunction, determined by aggregation or ATP release either spontaneously or in response to low-dose ADP or ristocetin, was not seen in any patient. These data suggest that the increase in access clotting is not the result of platelet hyperfunction induced directly by rHuEPO.

The cost of caring for end-stage kidney disease patients: an analysis based on hospital financial transaction records.

The costs of care for end-stage renal disease patients continue to rise because of increased numbers of patients. Efforts to contain these costs have focused on the development of capitated payment schemes, in which all costs for the care of these patients are covered in a single payment. To determine the effect of a capitated reimbursement scheme on care of dialysis patients (both hemodialysis [HD] and peritoneal dialysis [PD]), complete financial records (all reimbursements for inpatient and outpatient care, as well as physician collections) of dialysis patients at a single medical center over 1 year were analyzed. For the period from July 1994 to July 1995, annualized cost per dialysis patient-year averaged $63,340, or 9.8% higher than the corrected estimate from the U.S. Renal Data Service (USRDS; $57,660). The "most expensive" 25% of patients engendered 44 to 48% of the total costs, and inpatient costs accounted for 37 to 40% of total costs. Nearly half of the inpatient costs resulted from only two categories (room charges and inpatient dialysis), whereas other categories each made up a small fraction of the inpatient costs. PD patients were far less expensive to care for than HD patients, due to reduced hospital days and lower cost of outpatient dialysis. Care for a university-based dialysis population was only slightly more expensive than estimates predicted from the USRDS. These results validate the USRDS spending data and suggest that they can be used effectively for setting capitated rates. Efforts to control costs without sacrificing quality of care must center on reducing inpatient costs, particularly room charges and the cost of inpatient dialysis.