C. K. Jacob

Cytomegalovirus Infection in a Seroendemic Renal Transplant Population: A Longitudinal Study of Virological Markers

Background/Aims: The detection of viremia by polymerase chain reaction (PCR) in cytomegalovirus (CMV) infection in renal allograft recipients has been shown to have a predictive value for disease. However, its diagnostic utility in a population with high background seropositivity has not been defined. This prospective study was undertaken to assess the relationship of CMV DNAemia, and/or IgM seropositivity to CMV disease in a seroendemic transplant population. Methods: Consecutive patients undergoing renal transplantation between August 1997 and February 1998 were enrolled. Blood was sampled before transplantation from the donors and recipients for CMV serology and nested PCR for CMV DNA, and after transplantation from the recipients only at monthly intervals until 6 months. Patients were observed for the development of any CMV-like illness during follow-up. CMV DNA was quantitated using limiting dilution PCR on samples obtained from symptomatic patients at the time of illness and from asymptomatic patients at the end of their 6-month follow-up. Results: A total of 57 recipient-donor pairs were recruited. Immunosuppression was cyclosporine-based in 55 of 57 (95.6%). The CMV serologic status was D+R+ in 55 of 57 and D+R– in 2 of 57 pairs. PCR positivity indicating viremia increased from 5% before transplantation to 95% at 6 months after transplantation. Similarly IgM positivity reached 80% at 3 months and thereafter; positivity for any marker was 100% by 6 months. Viremia was sustained in over half the patients. The incidence of CMV-attributable disease peaked at 3 months, and was predominantly mild and self-limiting. Tissue-invasive disease appeared later in 4 patients (7%). Asymptomatic viremia was seen in 60–70% of patients at each sampling point. The positive predictive value (PPV) of PCR positivity for disease was 35–40%, and the negative predictive value (NPV), 90–100%. However, the high NPV was of use only in the early post-transplant period, negativity for markers declining rapidly with time. Quantitative assay showed significantly higher levels of CMV DNA in symptomatic patients (p = 0.01). A cutoff of 0.001 µg had a specificity of 95% and a PPV of 92.3% for symptomatic CMV disease. Conclusion: Qualitative tests to detect CMV DNAemia and IgM, although useful markers of viremia and active infection, have limited utility for the diagnosis of disease in a seroendemic transplant population. Quantitation of CMV DNAemia may play an important role in diagnosis in such a setting.

Leprosy and renal transplantation

Nine cases of leprosy in patients treated at a large renal transplant centre in South Asia are described. Three had leprosy diagnosed before transplantation and had either completed or were continuing chemotherapy at the time of transplantation. One showed exacerbation of undisclosed leprosy after transplantation. Five patients developed the disease for the first time 22 months to 12 years after transplantation. Immunosuppression did not adversely affect the treatment of leprosy in any of the patients though concurrent liver disease required cessation of rifampicin in one patient.

Haemolytic-uraemic syndrome complicating snake bite.

Anand Date, MD, Professor of Pathology, Christian Medical College Hospital, Vellore 632004, Tamil Nadu (India) Dear Sir, The triad of acute renal failure (ARF), thrombocyto-penia and haemolytic anaemia with fragmented erythrocytes (schistocytes) comprise the haemolytic-uraemic syndrome (HUS) [1]. In addition to its primary idiopathic childhood form, this syndrome can occur secondarily with viral and bacterial infections, oral contraceptive use and in pregnancy and in the puerperium [2]. Its occurrence after snake bite is not well known. During the period 1975–1983, 12 female and 12 male patients, with a mean age of 36 years (SD 14 years), were treated for ARF following snake bite at the Christian Medical College Hospital at Vellore in southern India. They had been referred for treatment from peripheral clinics 2–21 days after the onset of oliguria. Initially the patients had severe pain and swelling at the site of the bite and bleeding manifestations, most commonly haematu-ria with prolonged bleeding and clotting times. Oliguria or anuria developed within 24 h of the bite, and lasted for 4–47 days. The snake was identified by description as Vipera russelli in 7 cases. In the remainder, identification could not be made, although the symptomatology suggested that the Russell’s viper was involved in all cases and this is the only snake in this region whose bite is reported to cause ARF [3]. Results of laboratory investigations were as follows: Blood urea, mean 46.5, SD 25 mmol/l; plasma creati-nine, mean 967, SD 417 μmol/l; platelet count, mean 104, SD 92 × 10V1; packed cell volume, mean 0.27, SD 0.11; reticulocyte count, mean 5, SD 3%; total leukocyte count, mean 13.3, SD 4× 10V1; differential neutrophil count, mean 80, SD 8%. Schistocytes were present in the peripheral blood smears of 22 patients. Sixteen patients had HUS with anaemia, schistocytosis and thrombocyto-penia. Six patients had normal platelet counts when first examined 7 days or more after the bite, and there was no record of schistocytes in the peripheral blood smear in 2 cases. Absence of the complete triad could, in most cases, be attributed to incomplete or delayed investigation. Percutaneous renal biopsies performed in 15 patients showed cortical necrosis in 3 cases and acute tubular necrosis in the rest. Fibrin and platelet clusters were demonstrable in glomeruli and small calibre blood vessels in 5 of the 7 biopsies examined electron microscopically [4, 5]. Two patients were treated conservatively, 2 with hae-modialysis and the rest by peritoneal dialysis. One patient died of massive haematemesis soon after admission to hospital. Patients with cortical necrosis developed chronic renal failure, the others made a complete recovery.

The effect on patient management of temporary non-availability of immunofluorescence for renal biopsy reporting.

Delay in reporting the immunofluorescence findings on renal biopsies, owing to an interruption in supply of reagents, made possible a retrospective analysis of the effect of the lack of this information on patient management. Hospital case records of the 39 patients so affected were reviewed to determine what changes in their management took place after the immunofluorescence findings became available. The clinical, laboratory, and light microscopic findings in all except a case of pauci-immune crescentic glomerulonephritis allowed management decisions to be made that were not influenced by immunofluorescence findings. This was owing to correct prediction of the immunofluorescence findings, as in cases of IgA nephropathy presenting with recurrent haematuria; the adequacy of light microscopy in the interpretation of graft biopsies, in classifying lupus nephritis and in most cases of nephrotic syndrome; and the absence of entities identifiable only by immunofluorescence among these patients.

The pattern of medical renal disease in children in a south Indian hospital.

A retrospective study of children admitted to a south Indian hospital during an 11 year period showed that 70% of the renal diseases encountered in children in this region are of types which have a good prognosis. Post-streptococcal glomerulonephritis was the most common. The relative prevalence of steroid-sensitive nephrotic syndrome and different histological types of idiopathic nephrotic syndrome was similar to that in developed Western countries. Haemolytic-uraemic syndrome complicating bacillary dysentery was the most common cause of acute renal failure.

Calcium acetate versus calcium carbonate: Phosphate absorption studies in chronic renal failure

Summary: The aim of this study was to compare the alimentary phosphate‐binding capacity of calcium acetate to calcium carbonate in stable chronic renal failure patients who were not on haemodialysis. Intestinal absorption of phosphate and calcium was measured on three occasions in five patients with chronic renal failure who were not on maintenance haemodialysis. During each test period they received either no drug, calcium carbonate or calcium acetate (both containing 1g elemental calcium) in a randomized manner, along with a standardized meal. Intestinal contents were recovered after 10h by whole gut lavage, and phosphorus and calcium measured in meal and intestinal contents. Faecal excretion of ingested phosphorus increased from 13.85% in the absence of drug to 29.91% after calcium carbonate administration. Phosphorus excretion was significantly higher after calcium acetate (43.92%) compared to calcium carbonate (P<0.05). Less calcium was absorbed from calcium acetate than from equimolar amounts of calcium caronate (P<0.05). In patients with stable renal failure, calcium acetate is a better alimentary phosphate binder than calcium carbonate and binds more phosphorus for each mol of calcium absorbed.

Hereditary chronic nephritis in India.

Forty-six patients from 23 Indian families with hereditary chronic nephritis (HCN) with or without Alports syndrome are presented. The occurrence of this disease in diverse Indian races, communities and castes is now documented. Clinical and laboratory findings in these patients are similar to those reported from temperate regions.

Risk factors and outcome of hypertension in living related renal transplant recipients

Summary: Impaired allograft function is an important cause of hypertension in cadaveric renal transplant recipients. the risk factors for post‐tranplant hypertension in living related transplant recipients with inherent good graft functions are likely to be different and have not been studied. In addition, controversy surrounds any independent effect hypertension might have on renal allograft functions. Four hundred and seventy three living related renal allograft recipients were retrospectively analysed to study the risk factors for development of post‐transplant hypertension and its effect on graft outcome. Prevalence of hypertension was 76.1%. the presence of pre‐transplantation hypertension was the most important independent risk factor for development of hypertension after transplantation. This suggests an important role of retained native diseased kidneys as a cause of hypertension. Other risk factors included: cyclosporin A immunosuppression, patient age less than 40 years and the presence of renal insufficiency at last follow up. Hypertension did not have any effect on patient or graft survival during the mean follow‐up period of 20.1 ± 13.7 months; however, it was associated with an independent risk for the presence of renal insufficiency in the post‐transplant period.