Robert R. Riggio

Impact of renal donation. Long-term clinical and biochemical follow-up of living donors in a single center

Forty-six renal donors who responded to a questionnaire and two additional donors with nephrotic syndrome and renal insufficiency were studied. The mean age was 46 +/- 2.0 years (mean +/- SE). Duration of follow-up was 6 +/- 0.5 years. Serum creatinine levels increased from 1.0 +/- 0.03 mg/dl before donation to 1.2 +/- 0.04 mg/dl at follow-up. The incidence of proteinuria (more than 150 mg over 24 hours) was 39 percent. The serum creatinine level was 1.0 +/- 0.08 mg/dl and 1.2 +/- 0.06 mg/dl in the proteinuric and nonproteinuric groups, respectively. The incidence of hypertension was 31 percent with a serum creatinine level of 1.1 +/- 0.11 mg/dl and 1.2 +/- 0.07 mg/dl in the hypertensive and normotensive groups, respectively. One patient with nephrotic syndrome had proliferative glomerulonephritis. It is concluded that renal donation is associated with a minimal but statistically significant increment in serum creatinine levels. The incidence of mild hypertension and proteinuria is increased, but impact on renal function is minimal as assessed by serum creatinine determination.

Somatomedin and Growth after Renal Transplantation

Extract: Hormonal and metabolic factors which influence growth were studied in nine growth-retarded uremic children who received renal homografts. Post-transplant growth velocity based on bone age (GVBA) became normal in four (88–103%), accelerated in two (127–139%), and remained subnormal in three (18–50%). Serum somatomedin (SM), was very low in all children before transplant (0.39 ± 0.10 U/ml), but rose in each child after transplantation. Post-transplant somatomedin (0.84 ± 0.14 U/ml) was not significantly different from the somatomedin of eight healthy male control subjects matched for bone age (1.03 ± 0.16). Post-transplant GVBA was directly correlated (P < 0.05) with serum somatomedin and creatinine clearance (Ccr), but was not related to stimulated growth hormone response or to other variables of endocrine function. The data suggested that the growth failure in our patients with severe chronic uremia was due, at least in part, to lack of serum somatomedin. However, in four of five patients with persisting moderate azotemia (Ccr 11.8–42.5 ml/min/1.73 m2), subnormal growth continued despite relatively normalized serum somatomedin activity. Three of the four poorly growing azotemic patients had the highest average steroid dosages in the group (prednisolone > 9.1 mg/m2/24 hr).Speculation: If low serum somatomedin activity develops in the course of end stage renal disease in children, growth retardation may be the consequence. After renal transplantation normalization of serum somatomedin activity may be a necessary although not sufficient condition for the resumption of growth.

Hypercalcemia after renal transplantation

Hypercalcemia and hypophosphatemia after renal transplantation are described. Serum and urine calcium, phosphorus, creatinine and serum levels of parathyroid hormone (PTH) were followed in thirty-four patients who received transplants. Hypophosphatemia occurred in nearly all those with successfull transplants and correlated with the administration of oral hydroxide antacids. Clinical effects of phosphorus depletion included weakness, intention tremor, bone pain, pseudofractures and hypercalcemia. Treatment with oral phosphate reversed the abnormalities. The administration of aluminum phosphate gel did not induce hypophosphatemia. Hypercalcemia of 12 to 15 mg per cent necessitated subtotal parathyroidectomy in five patients, two of whom had oliguria and one polyuria due to hypercalcemia. The roles of parathyroid hyperplasia, phosphorus depletion, vitamin D therapy, steroid therapy and magnesium depletion in the evolution of post-transplant hypercalcemia are discussed.

Ototoxicity Induced by Furosemide

FUROSEMIDE is a diuretic that has achieved wide use because of its great potency as a saluretic agent and its low order of toxicity. We describe here transient ototoxic effects of high-dose furosem...

Systemic Lupus Erythematosus in Patients with End-Stage Renal Disease: Long-Term Follow-Up on the Prognosis of Patients and the Evolution of Lupus Activity

We studied the clinical course of 59 lupus patients with end-stage renal disease (ESRD) to determine their long-term prognosis and delineate the evolution of their lupus activity. The study population was predominantly female (86%) and young (mean age, 27.4 years), and they were observed for a mean of 6.5 years from the inception of dialysis. At the time dialysis was initiated, only 21 patients (35.6%) had clinically active systemic lupus erythematosus (SLE). The remaining patients progressed to ESRD despite the absence of clinical lupus activity. Lupus activity was clinically apparent in 55.4% of patients in the first year, 6.5% in the fifth, and none in the tenth year. In 45% of patients, lupus activity was clinically inactive at entry to ESRD and remained inactive throughout the observation period. Serological activity declined proportionally, but to a lesser extent than clinical activity. Cumulative patient survival was 81.1% and 74.6% at the fifth and tenth year, respectively, from the inception of dialysis treatment; similarly it was 78% at the fifth and tenth year after the transplantation. Graft survival was 60.4% at the fifth and 45.5% at the tenth year. No one had recurrence of clinical lupus nephritis in the graft for up to 16 years of follow-up. Fourteen patients died from either infectious or cardiovascular complications, but none from SLE per se. This long-term study with a large number of lupus patients confirms our previous findings that the progression of renal disease to ESRD may be mediated by nonimmunologic mechanisms, as well as immunologic insults.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal Segmental Glomerulosclerosis in Renal Transplants

This is a study of the incidence and clinicopathological significance of focal segmental glomerulosclerosis (FSG) in 154 renal allografts (22 biopsies, 128 nephrectomies and four necropsies) from 137 cadaveric and 17 living-related donors. FSG was identified in 18 grafts (11.7%) from 16 patients: six as recurrent FSG in four patients (two developed FSG in two consecutive transplants) and 12 as de novo FSG. The incidence of recurrent FSG in patients who had FSG as their original kidney disease was 30.8% whereas that of de novo FSG in patients who had renal diseases other than FSG was 8.7%. Histologically, recurrent FSG was characterized by mild degrees of obliterative arteriopathy of rejection and preferential involvement of the juxtamedullary glomeruli. Whereas, in de novo FSG, the occlusive vascular changes of rejection were severe and the glomeruli in the outer cortical region were mostly involved. Clinically, however, the differences between them were less clear, although nephrotic syndrome tends to occur more often and earlier in patients with recurrent FSG. Obliterative arteriopathy of chronic rejection and consequent glomerular ischemia appeared to be of major importance in the pathogenesis of de novo FSG in renal allografts.

Ocular complications in renal transplant recipients

Abstract The ocular complications in renal transplant recipients were evaluated in 44 patients and in 22 control patients with renal failure. Of the 44 patients 33 showed some ocular abnormality, but only posterior subcapsular cataracts which occurred in 34 per cent of post-transplant patients could be related to post-transplant corticosteroid therapy. There was no correlation between posterior subcapsular cataracts and either the duration of daily doses or total doses of corticosteroids in patients under 25 years of age in whom the incidence of posterior subcapsular cataracts tended to be higher than in older patients. There appeared to be a significant correlation between the duration of therapy and the total corticosteroid dose and the incidence of posterior subcapsular cataracts in the older age group.

Effects On In Vitro Lymphocyte Function

SUMMARY Serum of patients undergoing renal homograft rejection show increased levels of an α2-globulin. This serum, as well as an a.-globulin-enriched fraction of normal serum, alters in vitro lymphocyte activity as indicated by decreased 14C-thymidine uptake. These results suggest that the two a-globulins arc identical and that such a serum protein functions as part of an immunoregulatory system.SUMMARY Serum of patients undergoing renal homograft rejection show increased levels of an α2-globulin. This serum, as well as an a.-globulin-enriched fraction of normal serum, alters in vitro lymphocyte activity as indicated by decreased 14C-thymidine uptake. These results suggest that the two a-globulins arc identical and that such a serum protein functions as part of an immunoregulatory system.

Excellent outcome with a calcium channel blocker-supplemented immunosuppressive regimen in cadaveric renal transplantation. A potential strategy to avoid antibody induction protocols.

Many transplant centers routinely utilize monoclonal antibody or polyclonal antibody based induction protocols in recipients of cadaver renal allografts. Given the potential complications associated with antibody-based immunosuppression regimens (e.g., CMV disease), we tested the hypothesis that a combination of a calcium antagonist and a triple drug protocol (cyclosporine + prednisone + azathioprine) would be an effective substitute for antibody-based induction protocols in ensuring excellent patient and graft survival rates. Our postulate was tested in a prospective study of 52 consecutive recipients of cadaver renal allografts (44 first, 5 second, and 3 third grafts) utilizing nifedipine as the first line calcium antagonist. Nifedipine was selected over verapamil or diltiazem due to its lack of interference with the metabolism of CsA. Some of the significant outcomes of our prospective trial were (A) a cumulative patient survival rate of 98.1% for the 52 recipients at 18 months posttransplantation; (B) a cumulative allograft survival rate of 92.1% for the 52 consecutive cadaver renal allografts at 18 months; (C) a cumulative allograft survival rate of 100% at 18 months for the 24 of 52 renal allografts without delayed graft function following transplantation; and (D) a cumulative allograft survival rate of 86% at 18 months for the 28 of 52 renal allografts with delayed graft function. Of the 4 of 52 who lost their grafts, 2 grafts were removed following discontinuation of immunosuppressive therapy while the remaining 2 had primary nonfunction; and (E) the lack of a requirement for monoclonal or polyclonal antibodies for the treatment of acute rejection episodes in this patient population.

Clinical effects of bilateral nephrectomy

The effects of removal of all renal tissue on hematopoiesis, osteodystrophy, blood pressure regulation and metabolic functions are reviewed; and, the indications for, and results of, bilateral nephrectomy are discussed. Nephrectomy results in a more severe anemia in dialysis patients which is poorly responsive to androgen therapy. No differences were detected in the severity of osteodystrophy between nephric and anephric patients. However, bilateral nephrectomy can occasionally result in the acute onset of hypocalcemia. Blood pressure regulation must be accomplished in the absence of a functioning renin-angiotensin system. This is largely on the basis of volume, but changes in vascular tone may also be significant. Little is known about the metabolic consequences of nephrectomies. The effect on substances metabolized by the kidney is an area for further investigation. Kidney tissue should be preserved, if at all possible, and nephrectomy performed only for specific indications.