Tear flow study in renal transplant patients receiving cyclosporine A.

We studied tear flow in 23 renal transplant patients receiving cyclosporine A. Four minute Schirmer test was done once before and three times after starting cyclosporine A. Average tear flow was 9.7+/-0.9 before treatment and 15.9+/-1.1 at 1-2 months after renal transplant, 16.5+/-1.3 at 3-5 months and 17.6+/-1.4 at 8-10 months. Tear flow was significantly increased following oral cyclosporine treatment.

The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study.

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1- and 3-month protocol biopsies findings on 1-year renal allograft function in a prospective randomized study. Out of 102 living-donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2-h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short-term renal allograft function.

Role of duplex Doppler and power Doppler sonography in transplanted kidneys with acute renal parenchymal dysfunction.

The limited work published on the comparison of power Doppler sonography (PDS) and duplex Doppler sonography (DDS) in the assessment of acute renal allograft dysfunction has shown contradictory results. We compared the role of DDS and PDS in renal transplant recipients developing acute renal parenchymal dysfunction and correlated these findings with kidney biopsy, which was taken as the gold standard. Thirty post-renal transplant patients with acute graft dysfunction underwent Doppler sonography, DDS and PDS using an HDI 5000 ATL machine. Patients who developed graft dysfunction as a result of vascular, obstructive or other non-parenchymal causes were excluded. All patients underwent an allograft biopsy within 72 h of the sonography. Based on the biopsy findings, 24 patients were categorized as having acute rejection, and six patients as having no rejection. The overall sensitivity, specificity and accuracy of DDS for evaluation of graft dysfunction were 54.17, 33.33, and 50.00%, respectively, and that for PDS were superior with 87.50, 33.30, and 76.67%, respectively. The low specificity can be partially attributed to the small number of cases without rejection in our study population. We conclude that PDS is superior to DDS in screening patients with acute parenchymal renal dysfunction post-transplant. However, a normal PDS examination does not exclude the presence of acute rejection. Power Doppler sonography is a useful screening test for diagnosing acute rejection but a renal allograft biopsy remains the gold standard for diagnosis of this condition.

Visceral leishmaniasis: a rare cause of post-transplant fever and pancytopenia.

Despite the endemic distribution of visceral leishmaniasis in certain parts of our country, there are only a few reports of this infection in renal transplant recipients. We report one renal transplant recipient from non-endemic area with visceral leishmaniasis and graft dysfunction that responded to treatment with stibogluconate. The infection should be considered in the differential diagnosis of a febrile transplant recipient with pancytopenia and allograft dysfunction.

Central nervous system complications in renal transplant recipients in a tropical environment.

Renal transplant recipients are at risk of developing various infectious and non-infectious complications affecting the central nervous system (CNS). There is paucity of data regarding the spectrum of CNS complications and the epidemiology of infective agents varies according to geographical location. We retrospectively studied the spectrum of CNS complications seen in 792 renal allograft recipients followed up at this tertiary care centre in north India over a 19-year period. Autopsy findings of 78 allograft recipients who died in the hospital were also reviewed and included. The brain was examined in 22 of these patients. Overall, 79 (10%) patients developed some form of CNS dysfunction with a mortality rate of 60.8%. CNS infections occurred in 31 renal allograft recipients (3.9% of total) and accounted for the largest group (39.2%). Fungi were the commonest etiological agents (21 patients) and were associated with a 70% mortality, with cryptococcal meningitis occurring in 12, mucormycosis in six, aspergillosis in one, and other unusual fungal infections in the remaining two patients. All patients with mucormycosis had a fatal outcome. The second largest group comprised of patients with non-uremic encephalopathies (23 patients, 29.1%) with metabolic encephalopathy occurring in 13, toxic encephalopathy in nine and hypertensive encephalopathy in one patient) and was associated with an overall mortality rate of 60.9%. Cerebrovascular accidents occurred in 12 patients (15.2%) and were associated with a mortality of 91.7%. Other CNS complications included treatment related complications in four (5.1%), primary CNS lymphomas in three (3.8%), and miscellaneous complications in six patients (7.6%). Patients with non-cryptococcal fungal infections of the CNS, hepatic and toxic encephalopathy and those with cerebrovascular accidents had the worst outcome. There was no relationship between the development of infection or stroke and the type of maintenance immunosuppression used. We conclude that complications involving the CNS occur in 10% of all renal transplant recipients and are associated a with high mortality, warranting early diagnosis and aggressive treatment.

Impact of cyclosporine withdrawal on living related renal transplants: a single-center experience.

High treatment costs force the discontinuation of cyclosporine (CSA) in a vast majority of renal transplant recipients in India. The impact of CSA withdrawal among 108 living related renal transplant recipients 12.54 +/- 4.2 months after transplantation was studied retrospectively. In 83 patients, CSA was withdrawn over a 12-week period (group I). Azathioprine dosage was increased to 2 to 2.5 mg/kg/d, and prednisolone, to 30 mg/d 2 weeks and 1 week before starting CSA withdrawal, respectively. In the other 25 patients, CSA had to be withdrawn faster (mean, 28.52 +/- 14.18 days; group II). Twenty-nine rejection episodes (26.9%) were noted in 22 patients (20.4%; 19% in group I and 52% in group II; P: = 0.008). Fifteen group-I patients (18%) and 11 group-II patients (44%) died or lost their grafts (P: = 0.017). There was no difference in age, donor source, HLA matches, pretransplantation cross-match positivity, delayed graft function, immunosuppressive drug doses, rejection episodes, or prewithdrawal serum creatinine levels between the patients who did or did not develop acute rejection after CSA withdrawal. On follow-up, 10 patients (50%) died or returned to dialysis among the rejection group compared with 16 patients (18%) in the nonrejection group (P: = 0.007). The mean creatinine level at last follow-up was greater in the rejection group (3.97 +/- 2.54 versus 1.65 +/- 1.1 mg/dL; P: < 0.001). CSA withdrawal because of economic constraints carries a significant risk for acute rejection and death and/or graft loss in Indian living donor renal transplant recipients, even after 12 months.

Serum and urine nitrite and citrulline levels among patients with systemic lupus erythematosus: a possible addition to activity parameters?

Nitric oxide (NO) plays a significant role in the inflammatory process and has been implicated in several autoimmune disorders. This study was carried out prospectively to estimate the levels of nitrite and citrulline in the serum and urine, as surrogate markers of NO production, among patients with systemic lupus erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy volunteers were studied. Nitrite and citrulline were measured in serum and urine by spectrophotometry.Median serum nitrite and citrulline levels and urine citrulline levels were higher among patients as compared with controls (p < 0.05). Patients with skin involvement stood out and had higher median serum and urine citrulline levels (p < 0.05). Disease activity correlated with steroid dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05). Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine citrulline levels correlated with each other (p < 0.01). In the subset of 13 individuals with renal involvement, serum and urine citrulline levels correlated with each other (p < 0.01) as did urine nitrite and citrulline levels (p < 0.05).NO production is increased among patients with SLE, and this increase correlates with disease activity and dosage of steroids used. The addition of a urine test to measure NO production as a marker of disease activity using simple spectrophotometry can be a valuable adjunct to other tests, can obviate the need for drawing a blood sample for this purpose, and can be repeated as often as necessary.

Renal involvement in multiple myeloma: a 10-year study.

Renal involvement in 204 cases with multiple myeloma admitted over a 10-year period to this tertiary care center in north India was retrospectively examined. Renal involvement occurred in 55 cases (27%); the vast majority of whom (94.5%) had presented with renal failure and 7.3% had nephrotic syndrome. The diagnosis of multiple myeloma was made after admission in 51 of the 55 (92.7%) cases. Oliguria was seen in 23.6% and two-third patients required dialysis. Factors precipitating renal failure were identified in 53% and included dehydration (33%), hypercalcemia (24%), nephrotoxic drugs (16%), sepsis (9%), recent surgery (5%) and contrast media (2%), Severe anemia, hypercalcemia, Bence Jones proteinuria and skeletal abnormalities were more frequent in those with renal involvement. Patients with renal involvement were more likely to have a high tumor burden. The myeloma was of light chain type in 68% of those with renal involvement whereas IgG myeloma was commonest (57%) in those without evidence of renal disease. Renal histology was studied in 27 cases with myeloma cast nephropathy seen in over 60%. Tubulointerstitial nephritis was seen in 14% cases, 11% had amyloidosis, 7% had acute tubular necrosis and 3.6% each had nodular glomerulosclerosis and plasma cell infiltration. In 8 cases (14.6%), renal biopsy provided the first clue to the diagnosis of myeloma. Renal function improved in 33% cases. Only 22% of patients on dialysis survived over 6 months. Median survival in those with renal involvement was only 4 months. Development of unexplained renal failure in an elderly individual with normal sized kidneys, in association with disproportionate anemia even in the absence of skeletal lesions should alert the physician to the diagnosis of multiple myeloma.

CT in the evaluation of complicated autosomal dominant polycystic kidney disease.

PURPOSE: We retrospectively reviewed the CT findings in 24 cases of autosomal dominant polycystic kidney disease (ADPKD) to assess the role of CT in the diagnostic work-up of patients with complicated ADPKD. MATERIAL AND METHODS: Twenty-four patients with ADPKD underwent unenhanced and contrast-enhanced CT for flank pain, haematuria, or fever. The images were retrospectively reviewed for presence of complicated cysts, their morphological features and associated findings in the perinephric space/retroperitoneum. RESULTS: Cyst haemorrhage was present in all patients, seen as high-density cysts, which were mostly bilateral. Most of these cysts had sharply outlined contours, sharp interfaces with adjacent renal parenchyma, imperceptible walls, and homogeneous density, and did not enhance following i.v. contrast administration. However, a few haemorrhagic cysts (9 cysts in 6 patients) showed inhomogeneous density (n=7), dependent layering of high-density blood leading to fluid-fluid level (n=2), and contour irregularity (n=3). CT revealed presence of cyst infection in 6 cases; the involved cysts were larger (average size 4.2 cm) than adjacent cysts, had only a mildly increased or near water density, and showed wall thickening and enhancement. Other findings included air within the infected cyst (n=1), thickening and enhancement of peri- and paranephric fasciae (n=5), and abscesses in the posterior paranephric space and adjoining psoas muscle (n=2). In 2 other patients, although CT suggested cyst infection because of presence of wall enhancement, diagnostic needle aspiration revealed only sterile haemorrhagic fluid. In 1 case, CT revealed a soft tissue density enhancing mass in one of the cysts; this proved to be a renal cell carcinoma by fine-needle biopsy. Calculi were observed in 7 patients, and cyst wall calcification in 11 cases. CONCLUSION: A combination of unenhanced and contrast-enhanced CT allows correct diagnosis and differentiation amongst the various complications affecting patients with ADPKD. However, in a small subgroup of patients, it may not be possible to differentiate between haemorrhage and infection; such cases require diagnostic needle aspiration for diagnosis.

Treatment-related acute renal failure in the elderly: a hospital-based prospective study.

BACKGROUND: Elderly individuals need a host of diagnostic procedures and therapeutic interventions to take care of ailments. This prospective study was carried out to determine the magnitude of treatment-related acute renal failure (ARF) in the elderly in a hospital setting, to know about pathogenetic factors and to study the factors that could predict an adverse outcome. METHODS: All elderly patients (>60 years) admitted over a 12-month period were screened prospectively throughout their hospital stay for the development of ARF. RESULTS: Of 31860 patients admitted, 4176 (13%) were elderly. Of these 59 (1.4%) developed ARF in the hospital. Nephrotoxic drugs contributed towards development of ARF in 39 (66%), sepsis and hypoperfusion in 27 (45.7%) each, contrast medium in 10 (16.9%) and postoperative ARF occurred in 15 (25.4%) patients. These pathogenetic factors were responsible for ARF in different combinations. Amongst these combination of pathogenetic factors, radiocontrast administration (partial chi(2) 28.1, P<0.0001), surgery (partial chi(2) 14.89, P=0.001), and drugs (partial chi(2) 6. 22, P=0.0126) predicted ARF on their own. Nine patients (15.23%) needed dialytic support. Of 59 patients, 15 (25.4%) died, of those who survived, 38 (86.3%) recovered renal function completely and six (13.6%) partially. Mortality in the elderly with ARF was significantly higher than in those without ARF (25.4 vs 12.5%; chi(2) 8.3, P=0.03). Sepsis (odds ratio 43), oliguria (odds ratio 64), and hypotension (odds ratio 15) were independent predictors of poor patient outcome on logistic regression analysis. CONCLUSION: Incidence of treatment-related ARF in the elderly was 1.4%, with more than one pathogenetic factor playing a role in the development of ARF in the majority. Sepsis, hypotension, and oliguria were the independent predictors of poor patient outcome.

Isoniazid does not affect bioavailability of cyclosporine in renal transplant recipients.

Transplant recipients are predisposed to develop opportunistic infections such as tuberculosis, and isoniazid (INH) is used in most antitubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases with the concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are conflicting reports on a possible interaction between the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral) with slow acetylation status and also requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. There were no significant changes in CyA pharmacokinetic parameters including CyA trough levels, total CyA exposure and CyA clearance before and 2 weeks after instituting INH prophylaxis. There was also no statistically significant correlation between INH levels and changes in CyA pharmacokinetic parameters before and after administration of INH. Even after all post-INH pharmacokinetic parameters were adjusted for INH levels, the differences in the above pre- and post-INH parameters did not reach statistical significance. Renal function during the study period remained constant and there were no episodes of CyA toxicity or acute rejection during and up to 4 weeks of INH treatment. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in the bioavailability of CyA.

Long term effects of lithium on glomerular filtration rate in Indian subjects - a cross sectional study.

Glomerular filtration rate (GFR) was evaluated in thirty patients on lithium and in thirty healthy prospective kidney donors by single compartment, multiple sample plasma clearance method using (99m)Technetium diethylene triamine pentaacetic acid ((99m)TC-DTPA). Normality test revealed that dose and treatment duration were skewed and the coefficient of skewness were 0.067 (p< 0.0001) and 1.41 (p< 0.0001) respectively. Age was marginally skewed (p =0.04) for the control group. At 5% significance level, dose and creatinine were negatively correlated (r=-0.030), whereas age and duration were positively correlated (r =+ 0.53) (single tailed only). Duration and GFR seems to be negatively correlated (r = -0.23), however this correlation did not reach statistically significance level. In the present cross sectional study no significant difference in mean GFR was observed in lithium treated affective disorder patients when compared with the age matched normal subjects.

First report of tropical myositis and crescentic glomerulonephritis in a renal transplant recipient.

We describe a renal transplant recipient who presented with tropical myositis and acute allograft dysfunction 2(1/2) years after transplantation. Graft biopsy showed immune-complex crescentic glomerulonephritis. He was receiving only 7.5 mg/d of prednisolone for more than 2 months before presentation. Renal function did not improve despite treatment with antibiotics, methylprednisolone pulse therapy, and cyclophosphamide. He died of septicemia.

Successful management of pulmonary tuberculosis in renal allograft recipients in a single center.

BACKGROUND: Pulmonary infections, especially tuberculosis, are responsible for significant mortality and morbidity among renal transplant recipients in developing countries. Conventional diagnostic modalities are associated with a low yield, delaying specific therapy. METHODS: All patients transplanted within a 1.5-year period were prospectively followed-up for one year. Patients were on a cyclosporine-based triple immunosuppressive regimen. None received isoniazid prophylaxis, and those transplanted in the last seven months of the study period received daily cotrimoxazole. Patients exhibiting unequivocal evidence of pulmonary infections underwent further evaluation. Search for offending organisms was made by sputum examination and bronchoalveolar lavage (BAL). RESULTS: . Thirty-nine infection episodes were recorded in 34 patients. M. tuberculosis was isolated during 10 episodes, pyogenic bacteria and Pneumocystis carinii in 6 each, candida in 4, aspergillus in 3, cytomegalovirus (CMV) in 3, and nocardia and mucor in one episode each. More than one organism was isolated during five episodes. Bacterial pneumonia and tuberculosis were diagnosed in another seven and two patients, respectively, on the basis of a therapeutic response to specific chemotherapy. Over two thirds of the organisms were identified by examination of BAL fluid. BAL was useful in the diagnosis of tuberculosis and P. carinii pneumonia but was relatively insensitive for CMV and bacterial infections. An increased frequency of acute rejection and higher serum creatinine were factors that predisposed to infections. All patients with pulmonary tuberculosis made a full recovery. CONCLUSIONS: Tuberculosis and P. carinii are the most common nonpyogenic infections in the first year after transplantation in developing countries. An aggressive search for tubercle bacilli should be made using bronchoscopy and examination of BAL fluid in patients not responding to a short trial of antibiotics. A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuberculosis in patients on cyclosporine. We recommend routine prophylactic use of one single-strength tablet of cotrimoxazole daily for at least six months after transplantation.

Renal zygomycosis: an under-diagnosed cause of acute renal failure.

BACKGROUND: Invasive zygomycosis (mucormycosis) occurs predominantly in immunocompromised patients in whom it carries a grave prognosis. While renal involvement is not so uncommon in disseminated infection, isolated renal zygomycosis is rare. METHODS AND RESULTS: Forty-five patients with systemic zygomycosis were seen over a 12-year period from January 1986 to December 1997. Among these, 18 had renal involvement, nine with disseminated disease and nine with isolated renal zygomycosis. No underlying predisposing disease was identified in the majority of patients (72%). Renal involvement was confirmed at autopsy in 13 and by ante-mortem renal biopsy in five patients. The infection involved one kidney in five patients and was bilateral in the remaining. The manifestations included fever, flank pain, haematuria and pyuria with evidence of enlarged non-functioning kidneys on computerised tomography (CT). Of those with bilateral disease, 12 (92.3%) had anuric acute renal failure. Anti-fungal therapy was given to six patients (amphotericin B in mean total dose of 1.1 g) and of these only two with unilateral disease who also underwent nephrectomy survived while all the other 16 died. CONCLUSION: This study shows that renal zygomycosis has emerged as a cause of acute renal failure in the last decade since no patient with renal involvement was identified at our centre prior to 1986 even though autopsies have been done regularly in patients dying of unknown causes. Bilateral renal zygomycosis should be suspected in any patient who presents with haematuria, flank pain and otherwise unexplained anuric renal failure. Characteristic CT findings and an early renal biopsy can confirm the diagnosis and help in effective management of this serious disease.

Unpredictable cyclosporin--fluconazole interaction in renal transplant recipients.

BACKGROUND: Cyclosporin (CsA) is metabolized primarily in the liver by cytochrome P-450 enzymes. Concomitant use of fluconazole can increase CsA concentrations by inhibiting this enzyme system and the effect seems to be dose dependent, with no interaction noted when fluconazole is used in a dose of 100 mg/day. Two previous investigations studying this interaction while using higher doses of fluconazole have provided inconsistent results. Recommendations advising an empirical 50% CsA dosage reduction in these patients have not been tested in a prospective trial. METHODS: We studied six renal transplant recipients on CsA immunosuppression in a prospective, unblinded, crossover trial. Baseline renal functions, CsA area under the curve (AUC), Cmax, Cmin, CsA clearance, and Tmax were compared with those 2, 4 and 7 days after starting fluconazole orally in a dose of 200 mg/day. From day 8 onwards, patients reduced CsA dose by 50% and the above parameters were repeated on day 14. RESULTS: CsA AUC increased from 2887 +/- 1729 ng.h/ml on day 0 to 3842 +/- 1975 ng.h/ml on day 2 (P < 0.05), 4750 +/- 1718 ng.h/ml on day 4 (P< 0.01) and then decreased to 4052 +/- 1687 ng.h/ml on day 7 (P<0.01). Following CsA dose reduction by 50%, the mean AUC decreased significantly to 2330 +/- 1602 ng x h/ml (P<0.01). The Cmax showed a significant increase from 701 +/- 345 ng/ml on day 0 to 941 +/- 326 ng/ml (P < 0.01) on day 4 but decreased from 768 +/- 292 ng/ml on day 7 to 498 +/- 289 ng/ml on day 14, P<0.01. The mean Cmin increased from 207 +/- 138 ng/ml on day 0 to 274 +/- 168 ng/ml on day 4. No significant changes were observed in CsA clearance and Tmax. On repeated-measurement ANOVA, only the AUC and Cmax on day 4 of fluconazole were significantly higher than day 0 (P<0.001). There was a large interindividual variability in the degree of drug interaction between patients. CONCLUSIONS: Fluconazole given orally in a dose of 200 mg/day is associated with significant increase in bioavailability of CsA. The maximum effect occurs on day 4 after starting fluconazole. Although repeated monitoring of CsA Cmin is convenient as opposed to repeated determination of AUC, changes in Cmin may not be sensitive enough to pick up this interaction. The increase in bioavailability of CsA is unpredictable in individual patients and all patients should be monitored with AUC near day 4 of treatment to guide CsA dosage reductions.