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.

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.

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.

Critically ill elderly patients in a developing world--mortality and functional outcome at 1 year: a prospective single-center study.

PURPOSE: To study the mortality and outcome of critically ill elderly patients in a developing country with focus on nutritional and socioeconomic status. METHODS: A prospective study of 109 patients (215 screened) admitted consecutively to the intensive care unit from 2011 to 2012. Demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mechanical ventilation, Malnutrition Universal Screening Tool score, socioeconomic category, functional status, delirium, and length of stay were recorded. Telephonic assessment of outcome was done at 1 year. Appropriate statistical tests compared differences between subgroups. Multivariate analysis was performed on significant variables (P<.1) affecting mortality. RESULTS: At 12 months after discharge, 46.8% of patients (mean age, 76.5±9.6 years; APACHEII, 22.7±6.4; and intensive care unit stay, 7.8±3.4 days) had died. Risk factors for mortality at 12 months were APACHE II score (P<.001; odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1-1.3), severe malnutrition (P=.006; OR, 0.08; 95% CI, 0.01-0.48), and delirium (P=.03; OR, 0.32; 95% CI, 0.11-0.9). Risk factors for short-term mortality (at 28 days) were APACHE II score (P=.02; OR, 1.1 [1.0-1.2]) and premorbid functional status (P=.03; OR, 0.2 [0.1-0.8]). Kaplan-Meier survival analysis showed a significant association with malnutrition (log-rank test, P=.012) but not with socioeconomic category. Most (72%) of the survivors had a favorable functional status. CONCLUSIONS: Malnutrition, delirium, and APACHEII were risk factors for long-term mortality. Survivors had a good functional outcome. Appropriate quality of life tools for this population need to be developed.

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.

Acute demyelinating encephalomyelitis after anti-venom therapy in Russell's viper bite.

INTRODUCTION: Russell's viper is a commonly encountered venomous snake in India. Morbidity and mortality following envenomation and the treatment thereof are frequent. We report a rarely seen complication after a treated Russell's viper bite. CASE REPORT: A 36-year-old male farmer received 30 vials polyvalent anti-snake venom after a viper bite to his right leg. Improvement in initial hematemesis and circulatory shock was followed by acute renal failure managed with regular hemodialysis. He displayed no abnormalities on neurological examination at admission. Fourth day onwards his neurologic status started deteriorating with development of behavioral abnormalities, hemi-spatial neglect of left upper limb, paralysis of left facial nerve, left upper limb, and right lower limb. Acute disseminated encephalomyelitis was confirmed on magnetic resonance imaging (MRI) of brain with typical spectroscopic characteristics. High dose methyl prednisolone was administered and a rapid recovery followed. CONCLUSION: Russell's viper bite followed by treatment with antivenom may be complicated by the development of immune complex mediated demyelination and development of acute disseminated encephalomyelitis. MRI spectroscopy helps in early identification of demyelination and in a definite diagnosis. Treatment with corticosteroids was associated with resolution of symptoms in this case.

Clinical evaluation of selected Yogic procedures in individuals with low back pain.

The present study has been conducted to evaluate selected yogic procedures on individuals with low back pain. The understanding of back pain as one of the commonest clinical presentations during clinical practice made the path to the present study. It has also been calculated that more than three-quarters of the world's population experience back pain at some time in their lives. Twelve patients were selected and randomly divided into two groups, viz., group A yogic group and group B control group. Advice for life style and diet was given for all the patients. The effect of the therapy was assessed subjectively and objectively. Particular scores drawn for yogic group and control group were individually analyzed before and after treatment and the values were compared using standard statistical protocols. Yogic intervention revealed 79% relief in both subjective and objective parameters (i.e., 7 out of 14 parameters showed statistically highly significant P < 0.01 results, while 4 showed significant results P < 0.05). Comparative effect of yogic group and control group showed 79% relief in both subjective and objective parameters. (i.e., total 6 out of 14 parameters showed statistically highly significant (P < 0.01) results, while 5 showed significant results (P < 0.05).

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.

Functional assessment of immune markers of graft rejection: a comprehensive study in live-related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti-HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live-related donor renal transplantation. Flow cytometry-based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme-linked immunosorbent assay (ELISA) methods were employed to detect anti-HLA class I and class II antibodies and quantitative serum-soluble interleukin-2 receptor (sIL-2R) levels. The data revealed that patients with HLA class I-specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor-specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T- and B-cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody-negative group (T-B-, 82%, p = 0.05). Additionally, patients having non-donor but HLA-specific antibodies (FCXM-/ELISA+) had poor graft survival as compared to the antibody-negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN-gamma-producing T cells (19.16 +/- 7.4% median 17.50) as compared to their pre-transplant levels (5.68 +/- 1.63%, Median 5.20) and the non-rejecter group (5.97 +/- 4.39%, median 4.3, p = 0.0004). Similarly sIL-2 was significantly increased in AR episodes during the first month of transplantation (292 +/- 131.5 pmol/L) as compared to those with well-functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T-helper cells and quantitative analysis of sIL-2R offer additional valuable diagnostic and prognostic tools for follow-up of transplant subjects and a better alternative for functional assessment of immunosuppression.

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.

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.

A prospective randomized study to compare ultrasound-guided with nonultrasound-guided double lumen internal jugular catheter insertion as a temporary hemodialysis access.

UNLABELLED: Internal jugular venous catheters (IJVC) for hemodialysis are a commonly employed temporary vascular access for hemodialysis. Most hospitals still follow the use of blind technique, which uses anatomical landmarks. Even in the most experienced hands this procedure has a variable success rate. Ultrasound guidance can decrease the incidence of periprocedural complications and improve the success rate. In this randomized study we compared the procedure success rate and periprocedural complications in patients undergoing ultrasound guided vs. nonultrasound guided IJVC insertion for a temporary hemodialysis access. METHODS: All patients subjected to insertion of an IJVC between March 2004 and June 2004 were enrolled into the study, randomized to either the blind (group A) or ultrasound guided (group B) procedure, which uses a portable ordinary ultrasound machine without a needle guide. The aseptic Saldinger technique was used for catheterization in both the groups. Baseline characteristics of patient and periprocedural events were recorded. RESULTS: A total of 60 patients were randomized, 30 patients each in two groups. First attempt venous cannulation success rate was 56.7% in group A compared to 86.7% in group B. Chance of occurrence of adverse outcome was significantly more in the blind procedure (P=0.020). A post-procedure chest radiograph done in all patient showed no complications. CONCLUSION: Ultrasound guided procedure for internal jugular vein catheter insertion using an ordinary ultrasound machine was significantly safer and more successful as compared to the blind technique.

Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy.

BACKGROUND: Infectious diseases remain among the major morbid events in patients with end-stage renal disease (ESRD) on renal replacement therapy (RRT). In developing countries, tuberculosis (TB) has been found to occur more frequently in these patients than in the general population. Efficacy of isoniazid (INH) chemoprophylaxis has been seen in other situations, such as human immunodeficiency virus infection. However, studies on INH prophylaxis in ESRD patients on RRT are limited. METHODS: In this prospective randomized controlled trial, from April 2000 to June 2001, a total of 109 ESRD patients registered for renal transplant and accepted for maintenance hemodialysis in our hospital were included and followed up until June 2004 to assess the role of INH prophylaxis in preventing development of TB. At the time of acceptance for hemodialysis, 54 patients were assigned to receive daily INH for 1 year and 55 patients were assigned to the control group. Primary outcome was development of TB. Secondary outcome was INH hepatotoxicity. To evaluate the effect of INH prophylaxis on the development of TB, a Kaplan-Meier survival estimate was used to plot TB-free survival curve and log-rank test was used for comparison. RESULTS: Overall, TB was diagnosed in 27 patients during RRT, with an incidence of 24.8%. TB developed in 9 (16.7%) patients in the INH group and in 18 (32.7%) patients in the control group. There was a significantly lower incidence of TB in the INH group as compared with the control group. The risk ratio of INH vs. control group for development of TB was 0.40 (95% confidence index [CI], 0.17-0.92; P=0.032). In the INH group 27 (50%) patients and in the control group 17 (30.9%) patients developed some hepatic dysfunction. However, significant hepatitis that required discontinuation of INH developed in only 9 (16.7%) patients in the INH group. Furthermore, significant hepatitis also developed in 6 (10.9%) patients in the control group. The majority of patients with significant hepatitis in both groups (INH as well as control) were subsequently found to be positive for hepatitis B and/or hepatitis C viral infection. Mild hepatitis (which did not require discontinuation of INH) was seen in 18 (33.3%) patients in the INH group and 11 (20%) patients in the control group. Viral hepatitis infection was not found in any of the milder cases of hepatitis in either group. CONCLUSION: This study shows significant efficacy of INH chemoprophylaxis during RRT in preventing development of TB, when the INH was started during dialysis itself. INH chemoprophylaxis was safe and well tolerated in the majority of patients. However, mild hepatic dysfunction was common, both in the treatment as well as in the control group. As the incidence of viral hepatitis overall was high in our patients on RRT, it is difficult to identify INH-induced hepatitis in this clinical setting.