Disparity in utilization of combined kidney-liver transplantation in the United States.

BACKGROUND: Orthotopic liver transplantation (OLT) is performed as a definitive treatment of acute and chronic liver failure. The prevalence of acute and chronic kidney diseases is substantially higher in this population secondary to diverse etiologies. Combined kidney-liver transplantation (CKLT) is widely performed in some centers, even though there are no definitive studies which support or contradict this practice. METHODS: We comprehensively reviewed OLT as well as CKLT data from US transplant centers provided by United Network of Organ Sharing (UNOS). RESULTS: The incidence of CKLT as a percentage of total OLTs performed has been increasing, especially in the post-MELD era (2002 and after). Moreover, there is a great disparity among centers in regard to percentage of CKLTs to total OLTs. CONCLUSION: We conclude that there is much difference of opinion among US transplant centers as to indications for CKLT. A more scientific approach to this problem including studies to assess the role of kidney biopsy in determining renal outcome after OLT is needed.

Evaluation of proteinuria in healthy living kidney donor candidates.

BACKGROUND: Evaluation of living kidney donor candidates includes careful assessment for the presence or absence of kidney disease. Kidney donation has been considered to be at least relatively contraindicated if urinary total protein excretion is above the normal range. However, at the present time, there is no uniformly accepted level of urine total protein excretion that would exclude donation. Albumin excretion instead of total protein excretion as a criterion has not previously been evaluated. MATERIALS AND METHODS: This was a prospective observational study over a 3-year period in a single tertiary care center designed to assess current selection criteria for kidney donation with respect to urine total protein and albumin excretion. RESULTS: Twenty four percent (25 of 105) of healthy adult kidney donor candidates had elevated urinary total protein excretion rates (150 to 292 mg/24 h). Of these 105 candidates, 39 had simultaneous measurements of both urinary total protein and albumin. Although one-third (13/39) had elevated 24-hour urine total protein values, none had elevated urine albumin excretion. CONCLUSION: Measurement of albumin, the most common single protein found in urine, appears to be helpful in the evaluation of proteinuria in donor candidates. Many healthy adult kidney donor candidates have mildly elevated total protein excretion but normal albumin excretion. We believe that such patients should not be excluded from donation.

Decreased degradative enzymes in mesangial cells cultured in high glucose media.

Abnormalities in extracellular matrix degradation may play a pathogenetic role in diabetic nephropathy. Cultured renal mesangial cells are known to synthesize increased amounts of matrix proteins when incubated in high glucose media (e.g., 30 mmol/l). However, the effect of glucose loading on degradative enzymes is unknown. Primary cultures of rat mesangial cells were grown until confluent in the presence of fetal calf serum (FCS) and insulin (0.67 U/ml). Cells were then cultured for 7 days in plastic wells in either 10 or 30 mmol/l glucose media containing neither FCS nor insulin. Collagenase activity in media were determined by zymography and quantitative spectrofluorometry. Cathepsin B and D activities in cell extracts were measured by spectrofluorometry (using the fluorescent substrate Z-Arg-Arg-7-amido-4-methylcoumarin) and 125I-labeled hemoglobin digestion, respectively. Gelatin-degrading activity of live mesangial cells was also determined. mRNA levels for collagenase IV, cathepsin B, and cathepsin D were determined by Northern analysis. A major band of collagenase activity with a molecular size of 72 kDa was observed in all mesangial cell media. Exposure of cells to high glucose media resulted in significant reductions in collagenase and cathepsin B activities as well as impairment in gelatin-degrading activity. Collagenase IV and cathepsin B and D mRNA levels were also decreased by glucose loading. To exclude the possibility that glucose loading was injurious to cells, 3H-leucine uptake (as a measure of protein synthesis) and membrane alkaline phosphatase activity (as a biochemical marker of viability) were not affected by the high glucose condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of angiotensin II in glucose-induced inhibition of mesangial matrix degradation.

Accumulation of mesangial matrix in diabetic nephropathy is caused by increased synthesis and decreased degradation. We have previously demonstrated that incubation in high-glucose medium decreases mesangial cell collagenase activity (Diabetes 44:929-935, 1995). Because angiotensin II (AII) is involved in the pathogenesis of diabetic nephropathy, the present studies were performed to determine if AII mediates glucose-induced 1) inhibition of mesangial collagenase activity, 2) mesangial matrix accumulation, and 3) in-crease in transforming growth factor (TGF)-beta1 secretion in mesangial cells. The direct effect of high glucose on AII generation in mesangial cells was also determined. Primary mesangial cells from normal Sprague-Dawley rats were used in all studies. Collagenase activity in cell medium was determined using three methods: 1) zymography; 2) quantitative assay using fluoresceinated gelatin as substrate; and 3) a new enzyme-linked immunosorbent assay (ELISA) that specifically measures 72-kDa collagenase (MMP-2), the principal collagenase synthesized by mesangial cells. Matrix accumulation was estimated by immunoperoxidase assay on cell layers using anti-glomerular basement membrane (GBM) antibodies. TGF-beta1 and AII levels were determined by ELISA. Exposure of mesangial cells to 30 mmol/l glucose (high glucose) vs. 5 mmol/glucose (normal glucose) for 5 days resulted in a significant decrease in collagenase activity (25%) that was normalized by 10(-4) mol/l losartan, a type 1 angiotensin II (AT1) receptor antagonist. High glucose increased anti-GBM binding compared with normal glucose; this effect of glucose was reversed by losartan. Incubation of cells with 30 mmol/l glucose increased total TGF-beta1 secretion, which was also normalized by losartan. Addition of AII (10(-6) mol/l) for 24 h to the culture medium inhibited collagenase activity by 33%; losartan (10(-4) mol/l) blocked this inhibition of enzyme activity. Also, AII decreased collagenase (MMP-2) levels but stimulated TGF-beta1 secretion in mesangial cells. Finally, glucose increased mesangial AII generation in a concentration-dependent manner, with incubation in 30 mmol/l glucose increasing AII by 25% compared with 5 mmol/l glucose. We conclude that glucose increases AII production by mesangial cells, which results in stimulation of TGF-beta1 secretion, decreased matrix degradation, and increased matrix accumulation. These effects of AII are mediated by the AT1 receptor.

Spurious hyperphosphatemia due to hyperlipidemia.

A patient had hyperlipidemia associated with apparent hyperphosphatemia. Further tests on his serum and on the lipemic sera from 15 additional patients revealed a method-dependent overestimation of inorganic phosphorus values. The degree of overestimation was found to correlate positively with the serum triglyceride concentration. Unexplained elevation of the serum phosphorus level should alert the physician to the possibility of spurious hyperphosphatemia due to hyperlipidemia.

Subxiphoid pericardiostomy for hemodialysis-associated pericardial effusion.

Sixteen patients receiving maintenance hemodialysis in whom moderate-to-large pericardial effusions developed were treated with short-term drainage via a large-bore tube implanted into the pericardial sac. Drainage tubes were implanted using a subxiphoid approach (subxiphoid pericardiostomy) while the patient was under local anesthesia. In seven patients, triamcinolone hexacetonide was instilled into the pericardial sac through the drainage tube at regular intervals. In all patients, a drainage period of two to four days, with or without instillation of nonabsorbable steroids, was associated with resolution of the pericardial effusion. Only one recurrence of effusion was demonstrable over a follow-up period extending from three months to eight years (median, 4.2 years). Complications of subxiphoid pericardiostomy were minor (incisional hernia, wound infection, and small pneumothorax) and easily treatable. Our results suggest that short-term drainage via a surgically implanted drainage tube is an effective and safe treatment of moderate-to-large hemodialysis-associated pericardial effusion.

Asymptomatic, nonketotic, severe hyperglycemia with hyponatremia.

We describe five patients with asymptomatic, nonketotic, severe hyperglycemia (serum glucose concentrations between 45.8 and 92 mmol/L) in the face of renal insufficiency are described. As opposed to most of the previously described patients with hyperglycemic, nonketotic, hyperosmolar coma, our patients were hyponatremic. The lack of symptoms in our patients may be related to the absence of cerebral cellular dehydration. Aggressive treatment of hyperglycemia in such patients is unnecessary. Attention to the serum sodium level as well as to the serum glucose concentration will allow recognition of this clinical entity.

Fanconi syndrome associated with a non-ossifying fibroma of bone.

A 20-year-old man presenting with osteomalacia was found to have the Fanconi syndrome, as evidenced by hypophosphatemia with hyperphosphaturia, glycosuria in the presence of normoglycemia, and generalized aminoaciduria. After removal of a non-ossifying fibroma of the left tibia, the renal tubular abnormalities promptly resolved with subsequent healing of the osteomalacia. A humoral factor released from the tumor may have caused the disorder in proximal renal tubular cell transport.

Skin necrosis and protein C deficiency associated with vitamin K depletion in a patient with renal failure.

Skin necrosis similar to that induced by warfarin was seen in a patient who had never received the drug but who was vitamin K-deficient due to malnutrition and prolonged treatment with broad-spectrum antibiotics. He also had end-stage renal failure and was receiving prophylactic subcutaneous heparin therapy because of immobilization. His plasma protein C antigen level and, disproportionately, his plasma protein C functional activity were decreased. Both protein C values improved after vitamin K therapy, discontinuation of heparin, and initiation of hemodialysis. We surmise that skin necrosis occurred as a result of protein C deficiency caused by vitamin K depletion. Production of abnormal (descarboxy) protein C/protein S due to vitamin K deficiency and increased protein C inhibitory activity associated with renal failure and/or heparin administration may have contributed to the clinical picture. This rare but serious complication of a relatively common disorder, viz., vitamin K deficiency, reinforces the importance of vitamin K supplementation in malnourished patients who receive long-term antibiotic maintenance therapy.

Comparison of diltiazem and hydrochlorothiazide for treatment of patients 60 years of age or older with systemic hypertension.

This randomized, double-blind, parallel design trial compared the efficacy and safety of monotherapy with either sustained-release diltiazem or hydrochlorothiazide in 61 men greater than or equal to 60 years of age with a diastolic blood pressure (BP) between 94 and 104 mm Hg. BP, heart rate, laboratory blood and urine tests, left ventricular wall thickness and mass index (as estimated by M-mode echocardiography) and rate and type of ventricular premature complexes (via ambulatory electrocardiographic monitoring) were determined before, during and after drug treatment. Both drugs produced highly significant (p less than 0.001) decreases in supine and upright systolic and diastolic BP. The mean dosages of diltiazem and hydrochlorothiazide used were 260 and 52 mg/day, respectively; at these dosages, 80% of diltiazem-treated versus 71% of hydrochlorothiazide-treated patients achieved goal reduction in BP (supine diastolic BP reduction of greater than 10 mm Hg and to less than 90 mm Hg). Both drugs were well tolerated, although hydrochlorothiazide therapy was associated with multiple biochemical abnormalities not seen with diltiazem. Neither drug affected left ventricular mass index or the rate of ventricular ectopic activity. Diltiazem and hydrochlorothiazide are both effective and safe agents when used as monotherapy in older patients with systemic hypertension unaccompanied by other clinically significant cardiovascular disease.

Management of hypophosphatemia induced by high-flux hemodiafiltration for the treatment of vancomycin toxicity: intravenous phosphorus therapy versus use of a phosphorus-enriched dialysate.

Intensive high-flux hemodiafiltration is often used in the management of vancomycin toxicity. We describe two patients who developed hypophosphatemia as a consequence of this form of therapy. The first patient was treated with an intravenous phosphorus infusion. For the second patient, hypophosphatemia was corrected, during hemodiafiltration, with the use of a phosphorus-enriched dialysate. The latter dialysate was prepared by adding sodium phosphate salts to the "base concentrate" of a dual-concentrate, bicarbonate-based dialysate delivery system. This simple method was more efficient than intravenous therapy in ameliorating the hypophosphatemia secondary to aggressive hemodiafiltration treatment.

Transjugular renal biopsy in patients with liver disease.

Although transjugular renal biopsy has been used extensively in Europe, experience with its use in the United States has been limited. We report 25 patients who underwent both transjugular liver and renal biopsies in the same sitting and 4 patients who underwent only a transjugular renal biopsy. All 29 patients had both liver disease and renal abnormalities. Each patient was also believed to have a relative or absolute contraindication to a percutaneous renal biopsy (usually in the form of a bleeding abnormality). Transjugular renal biopsy yielded a quantity of tissue sufficient for diagnosis in all but 1 patient. The mean number of glomeruli obtained per biopsy was 19.4 +/- 12.2 (SD). Pathological diagnoses found were tubular injury in 5 patients, membranoproliferative glomerulonephritis in 5 patients, nephrosclerosis in 3 patients, diabetic nephropathy in 2 patients, immunoglobulin A (IgA) nephropathy in 2 patients, minimal change disease in 2 patients, end-stage renal disease in 2 patients, nonspecific changes in 1 patient, early glomerulosclerosis in 1 patient, tubular atrophy only in 1 patient, and normal renal histological characteristics in 4 patients. One patient with suspected IgA nephropathy had no histological diagnosis established because of a lack of glomeruli in the biopsy specimen. There were no instances of major bleeding from the perirenal area; however, a small perirenal hematoma was identified in 3 patients by postbiopsy computed tomography or sonography. Thus, based on our experience, transjugular renal biopsy appears to be a safe and effective procedure for establishing a histological diagnosis and is an attractive alternative biopsy method for patients with advanced liver disease and contraindications to conventional percutaneous renal biopsy.

Role of angiotensin II in diabetic nephropathy.

Considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor blockers (ARBs) can attenuate progressive glomerulosclerosis in disease models and can slow disease progression in humans. Because agents that interfere with Ang II action may decrease glomerular injury without altering glomerular pressures, it has been suggested that Ang II has direct effects on glomerular cells to induce sclerosis independent of its hemodynamic actions. To study nonhemodynamic effects of Ang II on matrix metabolism, many investigators have used cell culture systems. Glucose and Ang II have been shown to produce similar effects on renal cells in culture. For instance, incubation of mesangial cells in high-glucose media or in the presence of Ang II stimulates matrix protein synthesis and inhibits degradative enzyme (e.g., collagenase, plasmin) activity. Glucose and Ang II also can inhibit proximal tubule proteinases. Glucose increases expression of the angiotensinogen gene in proximal tubule cells and Ang II production in primary mesangial cell culture, which indicates that high glucose itself can activate the renin-angiotensin system. The effects of glucose and Ang II on mesangial matrix metabolism may be mediated by transforming growth factor-beta (TGF-beta). Exposure of mesangial cells to glucose or Ang II increases TGF-beta expression and secretion. Their effects on matrix metabolism can be blocked by anti-TGF-beta antibody or ARBs such as losartan, which also prevents the glucose-induced increment in TGF-beta secretion. Taken together, these findings support the hypothesis that the high-glucose milieu of diabetes increases Ang II production by renal, and especially, mesangial cells, which results in stimulation of TGF-beta secretion, leading to increased synthesis and decreased degradation of matrix proteins, thus producing matrix accumulation. This may be an important mechanism linking hyperglycemia and Ang II in the pathogenesis of diabetic nephropathy.

Paecilomyces peritonitis: case report and review of the literature.

While filamentous fungi are a rare cause of peritonitis in peritoneal dialysis patients, there is increasing recognition of Paecilomyces species as pathogens in such patients. We herein report a case of fungal peritonitis secondary to the filamentous Paecilomyces variotii species. The patient had a long and ultimately fatal course of illness despite catheter removal, discontinuation of peritoneal dialysis, recurrent intraabdominal abscess drainage, and prolonged courses of antifungal therapy. Our experience with this case and a review of the literature suggests that infection with this fungus can cause substantial morbidity and is probably best treated with prompt catheter removal, aggressive antifungal therapy and vigilant observation for complications.

Obstruction to venous outflow from the left lower extremity after renal transplantation.

Three patients with acute massive swelling of the left lower extremity occurring soon after placement of a renal allograft in the left iliac fossa are described. In each patient, obstruction to venous outflow from the left lower limb was documented by venography. We surmise that venous obstruction resulted principally from a combination of extrinsic compression of the left iliac vein by the right common iliac artery or by the allograft, and enhanced venous return from the allograft.

Use of a phosphorus-enriched hemodialysate to prevent hypophosphatemia in a patient with renal failure-related pericarditis.

We describe a patient who suffered from renal failure-associated pericarditis and underwent daily 3.5-hour hemodialysis treatments for 17 days. The initially elevated serum phosphorus level gradually fell to below normal on days 11 and 12 as a result of the intensive dialytic therapy. Phosphorus was added to the "base concentrate" of a dual-concentrate, bicarbonate-based dialysate delivery system on days 13 to 17. Because of this phosphorus-enrichment, we were able to maintain the patient's serum phosphorus levels within normal limits in spite of continued daily dialysis treatments.

Hypomagnesemia in continuous ambulatory peritoneal dialysis patients dialyzed with a low-magnesium peritoneal dialysis solution.

OBJECTIVE: Previous studies have shown a decrease in serum magnesium (Mg) concentration when continuous ambulatory peritoneal dialysis (CAPD) patients previously maintained on a 1.0-1.2 mEq/L Mg peritoneal dialysis solution (PDS) were dialyzed with a 0.5 mEq/L Mg PDS. However, the prevalence of hypomagnesemia in CAPD patients dialyzed with low-Mg PDS is unknown. DESIGN: A retrospective study to determine the prevalence of hypomagnesemia and the factors associated with its occurrence in CAPD patients dialyzed using a 0.5 mEq/L Mg PDS. SETTING: A CAPD unit in a large Veterans Affairs Hospital. PATIENTS: All our CAPD patients (33) enrolled over a 52-month period. RESULTS: All patients had serum magnesium levels higher than 1.25 mEq/L prior to use of low-Mg PDS. Hypomagnesemia (serum Mg < 1.25 mEq/L) developed in 21/33 patients (64%) when a 0.5 mEq/L Mg PDS was employed. Hypomagnesemia developed a mean of 8.2 months after beginning treatments. The duration of dialysis and the number of episodes of peritonitis did not differ between patients with and those without hypomagnesemia. Serum albumin levels were significantly lower in patients with hypomagnesemia (2.5 +/- 0.12 g/dL vs 3.2 +/- 0.12, p < 0.01). Magnesium supplements were given to 13 patients; following this therapy, serum magnesium values became normal. CONCLUSIONS: CAPD patients dialyzed with a 0.5 mEq/L Mg PDS may develop a considerable fall in serum magnesium level and may require magnesium supplements in order to restore normal serum values.

Predicting need for surgical drainage of pericardial effusion in patients with end-stage renal disease.

The best approach to treatment of pericarditis accompanied by substantial pericardial effusion in end-stage renal disease (ESRD) patients is unknown. In a review of our experience, we found that ESRD patients with moderate-to-large or large (circa 250 mL or larger) pericardial effusions usually failed to improve with intensive dialysis and ultimately required surgical drainage of the effusion. Multivariate analysis revealed that effusion size was by far the most important factor predicting need for surgery. Since early pericardial drainage obviates the risk of sudden tamponade, we recommend that surgery without prior intensive dialysis therapy be considered in such patients.

Removal of Foscarnet by hemodialysis using dialysate-side values.

Foscarnet is an antiviral agent widely used in the treatment of cytomegalovirus (CMV) infection. We describe a cardiac transplant patient, who while being maintained with hemodialysis because of tobramycin-induced acute renal failure, was given Foscarnet for disseminated CMV infection. Using dialysate-side clearance methodology, we found the dialyzer clearance of Foscarnet to be in the order of 89 ml/min.

Peritoneal sclerosis in continuous ambulatory peritoneal dialysis patients dialyzed exclusively with lactate-buffered dialysate.

Peritoneal sclerosis occurred in two patients treated by continuous ambulatory peritoneal dialysis (CAPD) using only lactate-buffered dialysate. Both patients had recurrent peritonitis and the second patient had multiple, minor abdominal operations. Patients receiving lactate-buffered CAPD are not immune from peritoneal sclerosis. Recurrent peritonitis and repeated abdominal surgery might be important causative factors.