S. Saxena

Diagnosis of glomerular haematuria : role of dysmorphic red cell, G1 cell and bright-field microscopy

Differentiation between glomerular and non-glomerular haematuria by observation of the changes in red cell morphology using phase-contrast microscopy is a well established technique. However, the method is not widely accepted in clinical practice because of controversy regarding the minimum percentage of dysmorphic red cells required to diagnose glomerular aetiology, as well as the need for specialized microscopes. Recently, a glomerular-specific morphological alteration of red cells has been described, which has the form of a doughnut shape with one or more blebs and which is termed the G1 cell. In the present double-blind prospective study 250 urine samples were examined without any knowledge of diagnosis. Haematuria was detected in 122 cases. The type of haematuria was characterized by counting dysmorphic cells and G1 cells separately, in each case using a phase-contrast microscope as well as an ordinary bright-field microscope with and without staining of urinary sediments. The results were later correlated with the confirmed diagnosis. The study showed that the G1 cell is more specific than the dysmorphic cell for the diagnosis of glomerular haematuria. Evaluation of both dysmorphic red cells and G1 cells can be done using bright-field microscopy with 100% specificity and sensitivities of 82 and 100%, respectively. It has been concluded that the ordinary bright-field microscope can be used for the diagnosis of glomerular haematuria with an efficiency similar to that of a phase-contrast microscope.

Effects of correction of metabolic acidosis on blood urea and bone metabolism in patients with mild to moderate chronic kidney disease: a prospective randomized single blind controlled trial.

Background. There are no controlled trials on the efficacy of oral bicarbonate therapy in patients with mild to moderate chronic kidney disease (CKD). This prospective randomized controlled study was done to evaluate the effects of correction of metabolic acidosis on renal functions and bone metabolism in this group of patients. Patients and Methods. Forty patients were randomized to treatment with oral bicarbonate or placebo for a period of 3 months. Investigations at baseline included venous pH, bicarbonate, renal functions, serum iPTH, and bone radiology. The treatment group (Group B) received daily oral sodium bicarbonate therapy at a dose of 1.2 mEq/kg of body weight. Their venous blood pH and bicarbonate levels were estimated weekly to keep blood pH near 7.36 and bicarbonate at 22–26 mEq/L by adjusting the dose of sodium bicarbonate. At the end of 3 months, all the tests were repeated in both groups.Results. After oral bicarbonate therapy (OBT), there was a significant decline in the rise of blood urea level in Group B associated with a sense of well-being in 50% patients. The rise in parathormone (PTH) was six times the baseline value in Group A and only 1.5 times baseline value in Group B, although not statistically significant. There was no significant change in total calcium, phosphorus, alkaline phosphatase, creatinine, total protein, or albumin levels. Conclusion. Correction of metabolic acidosis in patients with moderate CKD attenuates the rise in blood urea and PTH, which might prevent the deleterious long-term consequences of secondary hyperparathyroidism.

Results of conversion from triple-drug to double-drug therapy in living related renal transplantation.

Results of 34 recipients of living related renal allografts initially treated with cyclosporine, azathioprine, and prednisolone and later electively converted to AZA and PRED are presented. Thirteen (group A), 14 (group B), and 7 (group C) patients were converted before 9 months, between 9 and 12 months, and after 12 months, respectively. Thirty-four patients who were on AZA and PRED and had never received CsA served as controls. Of the 34 patients, 33 were HLA haploidentical with their donors and 1 was HLA identical. All patients received a mean 8.62 +/- 7.39 third-party blood transfusions. In the control group, 29 patients received haploidentical grafts. The number of blood transfusions given to this group was 7.09 +/- 9.13. Of the 34 patients receiving triple-drug therapy, 9 (26%) had acute rejection within 3 months after conversion, as compared with 5 (14.7%) in the control group (P > 0.05). Although 1 case had acute rejection before conversion, all recipients had stable graft function at the time of conversion. Of these 9 recipients, 7 had conversion over 4-7 weeks, while 2 had rapid conversion. Following treatment of the rejection episodes, 4 patients in the study group responded to therapy, as compared with 3 cases in the control group (P > 0.05). After a mean follow-up of 18.62 +/- 10.31 months (range 3-41 months) following conversion, 4 patients were normal, 4 had chronic rejection (mean serum creatinine = 3.0 mg/100 ml), and 1 was back on regular dialysis. Eventually, of the 34 patients who were converted from triple-drug to double-drug therapy, 25 were normal, 5 had stable chronic rejection, 2 were back on regular dialysis, 1 was retransplanted, and 1 died due to failed graft. At the end of follow-up, graft survival in the study group was 88.2%, as compared with 85.5% in controls (P > 0.05). We conclude that conversion from triple-drug to double-drug therapy is not without risk, even in living related primary renal transplantation. Degree of HLA matching, number of pretransplant blood transfusions, and rejection before conversion did not have any significant effect on rejections following conversion, and the graft loss following conversion is unpredictable.

Urinary Sporotrichosis in a Renal Allograft Recipient

Dr. Sanjay K. Agarwal, Assistant Professor, Department of Nephrology, Aiims, New Delhi-110029 (India) Dear Sir, We are reporting a case of urinary sporotrichosis in a renal transplant recipient. The patient had a radiolucent calculus with recurrent urinary tract infection. A 23-year-old male, having chronic glo-merulonephritis with end-stage renal failure underwent renal transplantation in July 1985. His mother was the donor with one haplotype match with the recipient. Postoperatively his renal function did not improve steadily. Ultrasound examination of the abdomen showed moderate hydronephrosis of the graft with narrowing of the lower end of the ureter. After confirming the finding on radionucleid scan on the 7th postoperative day, he was reoperated and a ureteroneocystostomy was done. Postoperatively he developed supra-pubic urinary leak which was managed conservatively. Following surgery his renal function improved slowly and on the 17th postoperative day serum creatinine was 106 μmol/l (1.2 mg/dl). He continued to have recurrent urinary tract infections which were treated according to the urine culture and sensitivity. On the 75th day following transplantation, a follow-up ureterocystoscopy was done which was essentially normal. However, his symptoms of lower urinary tract infection continued to persist even though the urinary cultures were repeatedly normal. In April 1986, although a plain radiogram of the abdomen was normal, the patient passed a stone per urethra, which was mainly made of ammonium phosphate with traces of calcium and oxalate. Keeping the possibility of a radiolucent calculus he was admitted for investigations. While in the hospital, he had acute retention of urine associated with enlargement of the graft which spontaneously got relieved within 12 h. However, a repeat ultrasonogram still showed hydroureterone-phrosis of the allograft with an echoic shadow at the lower end of the ureter. An antegrade pyelography performed at this time showed a dilated ureter (1.2 cm) and a stone at the lower end of the ureter. As the stone could not be dislodged, a percutaneus nephrostomy was done. Once the acute stage was over, he was operated for ureterolithotomy. During surgery multiple small yellowish calculi were found at the lower end of the ureter with a large stone 2 cm proximal to the vesicour-eteric junction

Clinical Profile and Course and Outcome of Late Acute Rejection Episodes in Living-Related-Donor Renal Allograft Recipients

We prospectively monitored clinical data and renal function at monthly intervals in 165 patients who had received living-related-donor renal allografts in our institution between January 1981 and December 1991 and had a functioning allograft for 1 year or longer. During a mean follow-up period of 47.2 (range 13-155) months, 32 patients (17.2%) developed late acute rejections, of which 14 (43.7%) were asymptomatic. Amongst the symptomatic late acute rejections, worsening of hypertension was the commonest finding, being present in 11 (61.1%) patients, followed by oliguria in 8 (44.4%) and weight gain in 7 (38.8%) patients. Of these 32 late acute rejections, as many as 28 (87.5%) showed a response to antirejection therapy with high-dose steroids: 5 (15.6%) a complete response and 23 (71.9%) a partial response. The response rate was 100% if it was the first acute rejection (20% complete and 80% partial), 78.6% if it was the second (14.3% complete and 64.3% partial), and no or only a partial response to treatment if it was the third acute rejection episode. On long-term follow-up, patients who had responded to to antirejection treatment had a significantly better graft survival as compared with nonresponding patients: 76 and 27%, respectively. Our observations suggest that routine monitoring of the renal function at frequent intervals is essential for early diagnosis and treatment of acute rejections, even during the late posttransplant period. The chances of a response to antirejection therapy are higher during the first episode of late acute transplant rejection as compared with second or a third late rejection event.

AZATHIOPRINE-INDUCED PURE RED BLOOD CELL APLASIA IN A RENAL TRANSPLANT RECIPIENT

Dr. Sanjay K. Agarwal, Assistant Professor, Department of Nephrology AIIMS, Ansari Nagar, New Delhi 110029 (India) Dear Sir, We report a case of pure red blood cell aplasia (PRBCA) induced by azathioprine (AZA) in a renal transplant recipient. K.L.T., a 30-year-old male, presented with chronic glomerulonephritis with end-stage renal failure in 1984 and underwent renal transplantation in March 1985. He was put on predniso-lone and AZA (2 mg/kg/day). On the 15th postoperative day he developed leucopenia. The dose of AZA was temporarily decreased to 1.5 mg/kg/day. In spite of his normal renal function, his haemoglobin (Hb) continued to remain low near 7-8 g% even 6 months after transplantation. Slowly his Hb picked up, but in November 1986 it dropped again to 8.3 g%. At this time detail investigations revealed: Hb 8.5 g%, total leucocyte count 6,300/mm3, reticulocyte count 3.3%, red cells showed anisocytosis, poikilocytosis and macrocytes. Mean corpuscular volume was 108 mm3. Red blood cell count was 5.2 million/mm3. Coomb’s test was negative. Bone marrow aspiration was normal. In view of the macrocy-tosis, a trial of vitamin B!2 and folic acid was given. His Hb slowly increased to normal within 2 months. The Hb remained normal till 8 months later, when it dropped to 8.2 g%. Treatment with vitamin B12 and folic acid was restarted, but this time his Hb did not increase. Considering AZA-induced toxicity cyclosporine was started in the dose of 2 mg/kg/day, and AZA was decreased to 0.75 mg/kg/day. His Hb increased to 12.5 g%, but to avoid long-term nephrotoxicity, cyclosporine was stopped, and the patient was put again on AZA (2 mg/kg/day). Within a few months his Hb dropped again to 7.6 g% with a reticulocyte count of 1.5%. Bone marrow biopsy at this time revealed normal myeloid and megakaryocytic elements but severe paucity of erythroid cells. AZA was stopped, and cyclosporine was started (2 mg/kg/day). His Hb became 12.6 g% in a month’s time. At this time a repeat bone marrow biopsy was normal. AZA can commonly cause leucopenia, predominantly granulocytopenia and mega-loblastic erythropoiesis [1], but PRBCA has also been reported in the past. The first 2 cases of PRBCA

Results of Renal Transplantation Using Living-Related HLA-identical Donors

Dr. Sanjay K. Agarwal, Assistant Professor, Department of Nephrology, A1IMS, Ansari Nagar, New Delhi – 110029 (India) Dear Sir, We present the results of 10 renal transplant patients on conventional immunosuppression who received transplant from living-related HLA-identical donors. Mean age of these patients was 33 years, and 9 out of 10 were males. The basic disease in 6 patients was chronic glomerulonephritis and 1 case each had polycystic kidney disease, diabetic nephropathy, bilateral renal artery stenosis and membranous glomerulopathy with chronic glomerulonephritis. Four patients belonged to blood group 0 and 2 each to A, B and AB. Each patient received a mean number of 50 haemodialyses before transplantation and 5-12 (mean 6) pretransplant third-party blood transfusions. Four patients had acute rejection (AR) episodes. Patient 1 had AR at the 3rd month, was antirejected with high-dose steroids, to which he did not respond, and lost his graft at the 5th month and subsequently died. Case 2 had 2 AR at the 13th and 20th month and lost his graft in the third year. Case 3 had 2 AR episodes at the 3rd and 6th week. He did not respond to steroid therapy followed by monoclonal antibodies and lost his graft at the 6th month. He was subsequently retransplanted. Case 4 had AR episodes at the 7th, 9th and 16th month and each time responded partially to steroids. He lost his graft at the 2nd year and died of renal failure. Case 5 who never had AR lost his graft at the 2nd year due to recurrence of membranous nephropathy. He was also re-transplanted. At the mean follow-up of 49 months (range 12144), 5 patients had lost their graft, 4 due to rejection and 1 due to recurrence of basic disease. Of these 2 died, 2 were retransplanted and 1 is being managed conservatively. HLA-identical donors for renal transplantation have been used since the early renal transplant period with excellent outcome [1]. The results have been the gold standard (1-year graft survival of nearly 90-95%) with which the results of HLA-nonidentical living-donor renal transplantations are compared [2]. Few studies have examined the potential benefits of cyclosporine (CsA) in HLA-identical transplants with inconclusive results [3,4]. Because of the controversy of the role of CsA in HLA-identical transplantation, most authors advocate only prednisolone and azathioprine (AZA) in this patient group [5,6].