Kidney transplantation: The journey across a century.

The Journey of kidney transplantation began a century ago with animal experiments and xenotransplants. The initial attempts of human to human kidney transplant were made by Yuri Voronoy, Jean Hamburger and several others between 1930 and 40s, but most of these were unsuccessful. The first successful live related kidney transplant between identical twins was performed at the Brigham Hospital in Boston in December 1953, by Joseph Murray and John P. Merrill, which paved the way for future live transplants. With the gradual improvement in the understanding of immunity and tolerance, the use of immunosuppression was attempted using irradiation and steroids, which gradually evolved over the decades to include azathioprine and cyclosporine. Discoveries of human leukocyte antigen by Dausset, complement dependent cross match by Paul Terasaki, and other developments in transplant immunology improved outcomes of kidney transplant. This journey was marked by new discoveries and improvements in surgical techniques including laparoscopic and robotic transplant surgery, better and safer immunosuppression, advances in transplant immunology, advent of the concept of brain death and deceased donor transplant program, and complicated transplants like transplants in highly sensitised recipients and ABO incompatible transplants. India was not far behind the rest of the world, and after a few unsuccessful attempts, the first successful transplant was done in CMC Vellore in 1971, which was followed by advancements in kidney transplants keeping in pace with the rest of the world.

To compare the outcomes of pancreaticojejunostomy and pancreaticogastrostomy reconstruction after pancreaticoduodenectomy: A prospective observational study.

Background: We have been in constant search of novel innovations to decrease the high morbidity after Pancreaticoduodenectomy (PD). Pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) are the two different methods of reconstruction after PD. However, the existing data is ambiguous in supporting either of them as the preferred technique of reconstruction. Methods: This was a single-center prospective observational study that included 64 patients who underwent PD over two years. We compared PG with PJ as a method of reconstruction after PD. The primary objective was to assess whether PG decreases the rate of postoperative pancreatic fistula (POPF) rates or not. Secondary objectives comprised analysis of perioperative outcomes, 30-day and 90-day mortality. Results: Pancreatic fistula was significantly lower in PG as compared to the PJ group (24% vs. 47%) with a p-value of 0.027. The incidence of clinically pertinent (grade B) fistula was only 3% in the PG group and 32% in the PJ group. PG group had a higher incidence of post pancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE). No statistically significant difference was seen between either group need for blood transfusion, re-exploration, re-admissions, ICU stay, or length of hospital stay, and 30-day and 90-day mortality. Pancreatic texture and high BMI were independent predictors for pancreatic fistula. Conclusion: PG when compared to PJ for reconstruction after PD, decreases the rate of POPF significantly; however, it is associated with an elevated risk of DGE and PPH. There was no difference in 30-day and 90-day mortality between both the treatment groups.

Cancer trends and burden among Armed Forces personnel, veterans and their families: Cancer registry data analysis from tertiary care hospital.

Background: Cancer incidence is rising across the globe. The incidence and patterns of various cancers among Armed Forces Personnel and Veterans is not known. We did the analysis of registry data maintained at our hospital. Methods: A retrospective analysis was performed of all patients registered at our hospital cancer registry between 01st January 2017 and 31st December 2019. Patients were registered with unique identification number. Baseline demographics and cancer subtype data were retrieved. Patients with histopathologically proven diagnosis and age ≥18 years were studied. Armed Forces Personnel (AFP) were defined as those who are in active service, and Veterans as those who had retired from service at the time of registration. Patients with Acute and Chronic Leukemias were excluded. Results: New cases registered were 2023, 2856 and 3057 in year 2017, 2018, 2019 respectively. AFP, Veterans and dependents among them were 9.6%, 17.8%, and 72.6% respectively. Haryana, Uttar Pradesh and Rajasthan represented 55% of all cases with male to female ratio 1.14:1 and median age was 59 years. The median age among AFP was 39 years. Among AFP as well as veterans, Head and Neck cancer was the most common malignancy. Cancer incidence was significantly higher in adults >40 years as compared to <40 years. Conclusion: Seven percent rise per year of new cases in this cohort is alarming. Tobacco-related cancers were the most common. There is an unmet need to establish a prospective centralized Cancer Registry to better understand the risk factors, outcomes of treatment and strengthen the policy matters.

Refeeding syndrome.

We report a case of a fifty-year-old male who was admitted with a three month history of increasing weakness, prostration, decreasing appetite and inability to swallow. The patient was a chronic alcoholic, unemployed, and of very poor socioeconomic background. The patient was initially investigated for upper GI malignancy, Addisons disease, bulbar palsy and other endocrinopathies. Concurrent management was started for severe electrolyte abnormalities and enteral nutritional supplementation was begun. By the fourth day of feeding patient developed severe hypophosphatemia and other life-threatening features suggesting refeeding syndrome. The patient was managed for the manifestations of refeeding syndrome. A final diagnosis of chronic alcoholic malnutrition with refeeding syndrome was made. Refeeding of previously starving patients may lead to a variety of complications including sudden death.

Tacrolimus (Pan Graf) in live related renal transplantation: an initial experience of 101 recipients in India.

BACKGROUND: Success of modern transplantation is in large part due to the successful development of effective immunosuppressive agents. The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus (Pan Graf, Panacea Biotec Ltd, India) has only been available in India for the last 2 years. This study was conducted to assess the safety and efficacy of tacrolimus in live related kidney transplantation. We report an initial experience of tacrolimus as de novo therapy in a live related renal transplantation program. MATERIALS AND METHODS: One hundred one consecutive recipients of a live renal allograft were commenced on triple immunosuppression consisting of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10-12 ng/mL in the first 3 months, 8-10 ng/mL in the next 3 months, and 5-8 ng/mL thereafter. All patients were followed up for a period ranging from 4 weeks to 24 months. The effect of this regimen on the incidence of graft rejection, graft survival, patient survival, and new-onset diabetes mellitus was evaluated. Any evidence of graft dysfunction was evaluated using a graft biopsy. RESULTS: There were 89 male and 12 female patients with mean age of 32.08 years. The incidence of acute rejection was 3.96%; 21.05% developed new-onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV)-positive; 77.7% of HCV-positive patients and 15.1% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival rate at the current follow-up was 92.07%. No graft was lost due to rejection. CONCLUSION: Tacrolimus is a safe and effective immunosuppressant in live related renal transplantation.

Primary signet cell adenocarcinoma of bladder.

Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Antegrade endopyelotomy in pelvic kidney.

Antegrade endopyelotomy was performed in a patient with pelvic kidney. Nephrostomy tube had been placed in the patient during a previous open pyelolithotomy. The nephrostomy tract was used for establishing percutaneous access. The ureteropelvic junction (UPJ) was balloon dilated and incised laterally under vision. At 3-month-follow-up renal dynamic scan showed no evidence of UPJ obstruction.

Fibrillary glomerulonephritis presenting as rapidly progressive renal failure in a young female: a case report.

Fibrillary Glomerulonephritis (FGN) is a rare clinical entity presenting in majority of patients with nephrotic range proteinuria, microscopic hematuria, impaired renal function and hypertension. The mean age of presentation is reported to be beyond 50 years with 50 patients developing end stage renal disease within a few years. A 28-year-old female presented to us with non-nephrotic range proteinuria, rapidly progressive renal failure (RPRF), microscopic hematuria and mild hypertension. The patient had undergone a renal biopsy at a peripheral center, which was reported as membranoproliferative glomerulonephritis (MPGN) and was being treated with steroids without any benefit. The patient on re-biopsy at our center was diagnosed as FGN on electron microscopy (EM). The patient responded to intravenous pulse methylprednislone and oral cyclophosphamide and is off dialysis for 10 months now. This case highlights the varied clinical and histological presentations of FGN which makes the disease difficult to diagnose more so, in a country like ours where EM is available in only a few centers. An accurate diagnosis aided by high index of clinical suspicion and EM can help in the initiation of appropriate therapy, thereby improving the outcome in this disease which otherwise has a poor prognosis.

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.

Left ventricular diastolic function in end-stage renal disease and the impact of hemodialysis.

Twenty-one patients (17 men and 4 women, aged 20 to 40 years) with end-stage renal disease (creatinine clearance persistently < 5 ml/min for > 3 months) were evaluated for left ventricular (LV) diastolic function by Doppler echocardiography before and after hemodialysis. Fifteen patients were on maintenance hemodialysis (group A) and 6 were studied before and after their first hemodialysis (group B). The following indexes of LV diastolic function were studied: (1) isovolumic relaxation time; and (2) Doppler indexes from mitral inflow signal--peak early velocity, peak late velocity (atrial), deceleration of early filling phase, and deceleration time of early filling phase. LV systolic function in groups A and B (LV ejection fraction 68 +/- 6 and 77 +/- 5%, fractional shortening 0.39 +/- 0.06 and 0.46 +/- 0.05%) was normal and did not change after hemodialysis. Group A had a prolonged isovolumic relaxation time of 80 +/- 22 ms, which decreased to 57 +/- 14 ms (p < 0.005). Deceleration time decreased from 248 +/- 58 to 184 +/- 38 ms (p < 0.00005) and the deceleration slope increased from 4.3 +/- 1.8 to 5.1 +/- 1.6 m/s2 (p < 0.005) after hemodialysis. In group B, isovolumic relaxation time decreased from 87 +/- 21 to 73 +/- 15 ms (p < 0.05), deceleration time decreased from 256 +/- 43 to 185 +/- 34 ms (p < 0.05), and deceleration slope increased from 3.5 +/- 0.8 to 4.2 +/- 1.1 m/s2 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of panel reactive antibody on live related donor kidney transplantation: Indian experience.

Serum samples from 95 recipients, transplanted with kidneys from live related donors, were tested for the presence of panel reactive antibodies (PRA) in pre- and post-transplant serum samples by the extended microdroplet lymphocytotoxicity test. The immunoglobulin class of antibodies was tested by treatment of serum with dithiothreitol. A significant correlation was found between the high PRA found in the 75 pretransplant sera tested and the subsequent rejection episodes. In addition, the level of pretransplant PRA activity was associated with graft survival in that patients with low PRA had significantly superior graft survival than those with high PRA. Furthermore, the present data show that patients with historical high PRA, but current low PRA, had graft survival similar to that in recipients who had moderate PRA in their current sera. High PRA patients had more often a positive crossmatch than patients with low PRA. The PRA level was also associated with prolonged waiting period. Immunoglobulin class of antibodies was related to graft acceptance in that the presence of IgM antibodies was not detrimental to transplantation. The results in the present study suggest that PRA of < 10% is negligible, while more attention should be paid to patients with PRA > 10%.

Acute renal failure following snakebite.

Eight patients with acute renal failure following snakebite were studied. Intravascular hemolysis and disseminated intravascular coagulation contributed to the development of acute renal failure in 6 patients. Direct nephrotoxicity causing acute renal failure is postulated in 2 patients, 1 of whom also revealed evidence of mild, disseminated intravascular coagulation. Three patients had histopathological lesions of acute symmetrical cortical necrosis and 3 had acute tubular necrosis. In 1 patient with acute tubular necrosis, in whom direct nephrotoxicity seemed to be responsible for renal failure, the striking histological feature was a uniform debasement and disappearance of tubular epithelium. In 2 patients with a clinical course of acute tubular necrosis, histological lesions could not be documented. All the 5 patients with acute tubular necrosis regained full recovery of renal function, 3 of them with the help of dialysis and 2 with conservative management. None of the 3 patients with acute cortical necrosis survived in spite of intermittent dialysis therapy.

Reduced urinary kallikrein excretion in human renovascular hypertension caused by nonspecific aortoarteritis and other disorders.

In this study urinary kallikrein excretion was measured using the kininogenase bioassay technique in 12 normal volunteers and 23 patients with angiographically-proven renovascular hypertension (RVHT). In 13 of these (group I), RVHT was due to nonspecific aortoarteritis (NSAA) and in 10 (group II) due to other causes. Urinary kallikrein (UKa) excretion was significantly lower in patients, with values still lower in NSAA. PRA was high in both the groups in comparison with controls; however, the levels were significantly lower in group I compared with group II. Finding of both UKa and PRA lower in group I is suggestive of long standing hypertension becoming volume dependent with nephrosclerotic changes in the kidney. These results point to decreased renal kallikrein-kinin system activity as a feature of NSAA that probably contributes chiefly to the maintenance of the hypertensive state. Normalisation of BP with restoration of UKa and PRA towards normal in three patients of group I and five in group II further support the role of UKa not only when over activity of renin-angiotensin system is responsible for RVHT as in group II but also in group I when the hypertension becomes volume dependent.

The prevalence of microalbuminuria in diabetes: a study from north India.

Geographic/population variation in the prevalence of diabetic nephropathy is well recognised. In a study of 'native' Indians, we screened 102 non-proteinuric diabetes mellitus patients (64 NIDDM, 38 IDDM; mean age and diabetic duration 48.7 and 6.5 years, 21.6 and 6.2 years, respectively) with blood pressure less than or equal to 170/105 and without congestive heart failure, ketonuria or urinary tract infection, for the presence of microalbuminuria (albumin excretion rate greater than 20 micrograms/min). Fifty-six patients (34 NIDDM, 22 IDDM) also underwent detailed fundus examination. Seventeen NIDDM (26.6%) and 3 IDDM (7.9%) patients had microalbuminuria. Glycated hemoglobin was significantly higher in microalbuminurics in the NIDDM group (P less than 0.05). Diabetic retinopathy tended to occur more frequently in microalbuminurics (NIDDM and IDDM).

Immunopathology, extent and course of glomerulonephritis with crescent formation.

Ten out of 66 cases of glomerulonephritis (GN) with variable crescent formation appeared to be of post-streptococcal origin. Immunofluorescent studies of biopsies from 42 of the patients showed findings suggestive of immune complex glomerular injury in 86% whilst there was no evidence of immunologic or nonimmunologic injury in the remainder. Anti-GBM GN was not demonstrable, although it can not be certain that there were no cases amongst the patients whose biopsies were not examined by immunofluorescence. Conservative measures were adequate for the treatment of cases with less than 50% crescents. In the others, with greater than or equal to 50% crescents, appreciable improvement was observed with anticoagulation, immunosuppression and dialysis. The mortality was 30% in cases with 50-80% and 65% in cases with greater than 80% crescents. No appreciable difference in survival was observed between post-streptococcal and idiopathic cases. The single most important factor in prognosis, regardless of etiology, appeared to be the extent of crescent formation. Tubulo-interstitial damage was contributory. Necrotizing angiitis, present in 4 cases, affected the course adversely.

Prognostic significance of renal angiitis in systemic lupus erythematosus (SLE).

Analysis of 80 cases of SLE with renal involvement revealed the following. Angiitis involving arterioles and interlobular arteries was observed in 17 out of 42 cases with diffuse proliferative lupus GN. This was not observed in other types of lupus GN. Out of 17 cases of angiitis, 7 were complicated by thrombosis. Irregular deposits of immunoglobulins and complement were demonstrated in the vessel walls and in luminal thrombi and suggested an immune-complex origin. Fibrinogen was also demonstrable frequently. The vascular lesions were associated with severe glomerular and tubulointerstitial injury and a poor prognosis. A relatively favorable outcome was observed in SLE without renal angiitis.

Influence of HLA compatibility on renal graft survival using live unrelated & cadaver donors in India.

BACKGROUND & OBJECTIVES: Living unrelated donor (LURD) renal transplantation has shown a rising trend over the last 5 yr at our center following the passing of The Transplantation of Human Organs Act by the Government of India in 1994. In this paper, the results of LURD and cadaver (CAD) donor renal transplantation are compared. We have also looked into factors that have a bearing on graft survival such as the extent of HLA mismatch (MM), infections, acute rejections (AR), donor age and sex. METHODS: A total of 42 LURD and 25 CAD renal transplants performed between March 1994 and February 1999 has been included in the study. HLA typing, panel reactive antibody (PRA) screening and T and B cell cross match assay were performed by the complement dependent cytotoxicity (CDC) method for all patients. RESULTS: The graft survival rates were generally higher in the LURD category as compared to the CAD group and were significant at 6 month period (90 vs 56%, P = 0.002). A follow up of the patients up to 60 months revealed a matching effect since the 3, 4 allele MM group had better survival rates as compared to the 5, 6 MM group. Twenty six of the 67 recipients (39%) experienced episodes of acute rejection (AR). Patients with 3, 4 MM had fewer such episodes than those with 5, 6 allele MM (P < 0.05). Of the 32 deaths, 20 were those with a functional kidney, of which 15 were caused by severe infections. INTERPRETATION & CONCLUSION: Better HLA matching ensures fewer episodes of rejection and better long term graft survival in comparison to the poorly matched grafts. The graft survival for LURD recipients was appreciably higher than that of CAD recipients.