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.

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.

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.

An unusual case of bilateral renal enlargement due to primary renal lymphoma.

Primary renal lymphoma is an uncommon variant of extranodal non-Hodgkin's lymphoma. Manifestations are usually nonspecific hematuria, fever, flank pain, and renal insufficiency. Pathological data are scanty; few reports indicate it has a very poor prognosis. We describe a child with bilateral symmetrically palpable kidneys, low-grade pyrexia, and arthralgia. Clinically, diagnosis was missed partly due to the fact that bilateral large renal tumors commonly produce asymmetric renal swelling, renal dysfunction, and hematuria which were absent in this case and partly due to rarity of the condition. However, radiological investigations combined with renal histology helped in establishing diagnosis in the present case.

A comparative clinical trial of Chincha kshara and Kadali kshara on Amlapitta.

A clinical trial was carried out on 30 patients of Amlapitta aged between 20 to 35 years with complaints of Avipaka, hrit-kanthadaha, tikta-amlodgara, utklesa, udarasula, adhmana and aruchi, who were registered from OPD and IPD of Gopabandhu Ayurveda Mahavidyalaya, Puri. They were equally divided into three groups Chincha kshara, Kadali kshara and placebo (who were administered with fresh wheat powder) for 30 days in a dose of 500 mg thrice daily with water. Investigations was done in order to exclude upper gastrointestinal tract ulcer, carcinoma in stomach, cholecystitis, carcinoma gall bladder, and heart diseases. The clinical assessments were carried out on the 30(th) day by subjective and objective parameters and it was inferred that both Chincha kshara and Kadali kshara were effective and reduced the symptoms of amlapitta. Chincha kshara was found to be more effective than Kadali kshara. The study shows the effect of Chincha and Kadali kshara which led to cure in 4(40%) and 3(30%) patients respectively, and maximum improvement in 4(40%) and 5(50%) patients affected with amlapitta disease, respectively. No untoward effect was noticed due to administration of ksharas during the clinical trial period.

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.

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.

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.

A case of chronic myeloid leukemia complicated with minimal change nephrotic syndrome.

We present a 28-year-old patient with chronic myeloid leukemia (CML) in chronic phase complicated with nephrotic syndrome. The bone marrow cells revealed the presence of Philadelphia chromosome, the cytogenetic hallmark of CML, that results from a balanced, reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11). This reciprocal translocation leads to the formation of the BCR/ABL fusion gene, the presence of which was confirmed using the highly sensitive fluorescence in situ hybridization technique. The renal biopsy was compatible with minimal change nephrotic syndrome. To the best of our knowledge, this is the first case of minimal change nephrotic syndrome associated with CML before the administration of any therapy.

Pulmonary mucormycosis in a diabetic renal transplant patient.

A 50-year-old male, diabetic, post transplant patient had recurrent pneumonia. The first episode responded well to antibiotics, while on the second occasion he had a necrotising pneumonia, which developed into a thick-walled cavity. Despite antibiotics, his condition rapidly deteriorated precluding bronchoscopy or percutaneous biopsy. Post-mortem lung biopsy revealed typical hyphae of mucormycosis.

Hepatitis C virus related cryoglobulinemic glomerulonephritis.

A 46 years male presented with skin rash and acute nephritic syndrome. He had history of jaundice four months back. Rheumatoid factor and cryoglobulins were present in the serum. Although anti-HCV antibodies were negative, HCV RNA was detected by polymerase chain reaction. Kidney biopsy showed membranoproliferative glomerulonephritis and thrombi in the lumen of the glomerular capillary loops. His renal functions improved with steroids.

Chronic interstitial nephritis following parenteral copper sulfate poisoning.

A 21-year-old male patient was admitted with acute renal failure and intravascular hemolysis following suicidal parenteral copper sulfate poisoning. He developed metabolic acidosis and septicemia; and was treated with intensive hemodialysis, blood transfusions and antibiotics. After remaining anuric for 4 weeks, his urine output gradually increased. However his renal functions improved only partially. Renal biopsy done 8 weeks after the episode showed chronic tubulo-interstitial nephritis (CIN). This is the first reported case showing CIN following acute copper sulfate intoxication.

Total dose iron infusion: safety and efficacy in predialysis patients.

Iron deficiency anemia is not uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total dose infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0 g/dL and serum ferritin < 200 ng/mL were selected. Patients with active bleeding and acute liver disease were excluded. All patients were on oral iron 100 mg/day. None of the patients were on erythropoeitin. 11 patients (6 males and 5 females), aged 45.9 +/- 15 yrs, were suitable. Hb was 5.9 +/- 1.0 g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25 mg in 100 mL normal saline was administered over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600 mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0 g/dL and serum ferritin was 362 ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.

Spectrum of renal diseases in Indian adults.

INTRODUCTION: Inspite of nephrology as a specialty since seventies, there is still paucity of data regarding the spectrum of renal diseases in India. Available literature from few hospitals shows data on specific clinical syndrome of renal diseases or specific renal diseases rather than the overall spectrum as a whole. This information will be useful for better resource management. MATERIAL AND METHODS: We studied spectrum of renal diseases among 14,796 patients presenting for the first time to nephrology outpatients between January 1987 to Oct. 1998. Majority of patients in our clinic were adults. Patients 14 years or below who mostly attend pediatric renal unit of the hospital were excluded from the analysis. Till 1991, the study was retrospective but after 1991, patients were followed prospectively. Patients were grouped according to classical renal syndrome. After the initial presentation, patients were followed subsequently till their last follow-up in the clinic or till the time of reporting the present data. RESULTS: Mean age of patients was 38.69 +/- 15.5 years with male predominance in majority of presentations. Chronic renal failure (CRF), nephrotic syndrome (NS), nephritic syndrome and hypertension were the four common presentations seen in 47.8%, 15.03%, 4.6% and 4.9% cases respectively. Other presentations were acute renal failure (1.9%), urinary tract infection (2.9%), stone disease (4.6%), obstructive uropathy (2.1%), isolated haematuria (1.2%) and asymptomatic urinary abnormalities (0.3%). Chronic glomerulonephritis was seen in 49.4% cases of CRF followed by diabetic nephropathy in 28.4% cases. Of the nephrotic syndrome cases, primary glomerulonephritis was seen 58.5% cases, of which minimal change disease was the commonest cause in 38% cases. Of the secondary glomerular diseases, diabetic nephropathy was commonest cause of NS (53%) followed by amyloidosis (16.4%) and lupus (8.3%). Tuberculosis was the commonest cause of renal amyloidosis seen in 50% cases. Of the nephritic syndrome, post-infective glomerulonephritis was commonest cause followed by rapidly progressive glomerulonephritis being the second commonest cause. In the hypertensive group, essential hypertension was the commonest cause followed by renovascular hypertension. CONCLUSION: It is the first large study of its kind presenting the spectrum of renal diseases in the tertiary-care government hospital of the country and we expect the disease pattern to be reasonably similar in other similar government hospital of the country. Chronic renal failure, nephrotic syndrome and diabetes are three major diseases, with which we have to deal maximum. As CRF in young male patients is the largest load, with its wide social and economical implications in the Indian context, we must gear up to organise ourselves for providing the best possible care to these patients with the limited resources.

Role of supravital staining of urine sediment and bright field microscopy in diagnosis of acute renal failure in bedside medicine.

BACKGROUND: An early accurate etiological categorization of acute renal failure (ARF) into acute glomerulonephritis (AGN), acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) is very important in clinical medicine. METHODS: To evaluate the efficacy of a simple, cheap supravital staining method developed in our laboratory, we examined urine of 32 cases of ARF at their initial presentation in oliguric phase, which were later biopsied. The stain consisted of 1% crystal violet and 0.5% safranin in normal saline. The coverslip preparations of coded and stained urine sediments were examined under ordinary bright field microscope (BFM) by two independent observers. RESULTS: The renal biopsy showed 12 cases of AGN, 12 ATN and 8 AIN. The diagnosis could be predicted by supravital staining method in 75% cases with 95% uniformity among two observers with a sensitivity of 85.7% for AGN followed by AIN (80%) and ATN (75%). CONCLUSION: Thus this simple supravital staining technique can be used with ordinary BFM for accurate urine sediment analysis in cases of ARF in bedside medicine.