Rare complications of heart transplant: Autopsy findings.

BACKGROUND: Heart transplantation has evolved as the only treatment option for patients with refractory heart failure. CASE PRESENTATION: We here, report two unusual complications that developed following cardiac transplant to which the recipients succumbed. Post mortem conducted revealed the cause of death as severe antibody mediated rejection in one case and ruptured mycotic aneurysm of ascending aorta in the second recipient. CONCLUSION: Hence, autopsy remains the key procedure that can help establish the cause of death after cardiac transplant. It is also imperative for clinicians to have awareness and high index of suspicion for early detection of the ongoing complications and intervene either surgically or medically to prevent catastrophic events.

An Unusual Clinical Manifestation of Plasmablastic Lymphoma in a Renal Transplant Recipient.

Plasmablastic lymphoma is a rapidly progressive CD20 negative large cell non-Hodgkin lymphoma with poor outcome. It occurs mostly in immunocompromised individuals and has a predilection for extranodal sites. They need to be differentiated from other entities sharing similar morphological features like poorly differentiated carcinoma, Burkitt's lymphoma, Alk positive large B cell lymphoma, Diffuse large B cell lymphoma, and anaplastic myeloma. EBV negativity in recipients, type, intensity, and duration of immunosuppressives used are certain risk factors in development of posttransplant lymphoproliferative disorders. High index of suspicion can help clinch the diagnosis early and prevent catastrophic consequences. Our renal transplant recipient presented with complaints of pain abdomen and malena for which he underwent exploratory laparotomy. Diagnosis was established on histopathology and timely treatment initiated reverted the disease.

Pneumoperitoneum needle vs. introducer needle: Comparison of complications and short-term outcomes in percutaneously inserted peritoneal dialysis catheters in naïve abdomens.

Percutaneous peritoneal dialysis catheter (PDC) insertion for continuous ambulatory peritoneal dialysis (CAPD) entails a higher risk of complications such as bowel injury, vascular injury, and catheter migration compared to the surgical insertions. We conducted a comparative analysis of two techniques of peritoneal entry for PDC insertion by Seldinger technique. We performed a retrospective review of 426 percutaneously inserted PDCs in nonobese naïve abdomens for CAPD at two tertiary care teaching hospitals in India over 6 years. Comparison of various mechanical complications, and short-term catheter survival was done between use of introducer needle (Group "I") and spring-loaded pneumoperitoneum (Veress) needle (Group "V"). Group "I" to "V" patient ratio was 277:149. Group "I" had heavier patients (p = 0.03) whereas "V" group had a dominance of diabetes (p = 0.009) and prior hemodialysis patients (p = 0.03). At 3 months, the odds of mechanical complications (OR = 0.27, p = 0.004), PDC migration (OR = 0.18, p = 0.02), and omental wrapping (OR = 0.13, p = 0.04) were less in "V" group. No bowel injury occurred with Veress needle use. At 6 months, "V" group had higher odds of event-free sustained PDC tip position (OR = 0.39, p = 0.003), and catheter survival (p = 0.03), and the cumulative events were lesser too (p = 0.002). Refractory peritonitis and deaths with functioning catheter were comparable between both the groups. In this first-of-its-kind study, spring-loaded Veress pneumoperitoneum needle use was safer, entrusted sustained PDC tip position in pelvis, and had a better catheter survival compared to use of introducer needle for peritoneal entry in percutaneously inserted PDCs. These findings should be confirmed by a randomized controlled study.

Peritoneal Dialysis Catheter Insertion by Nephrologist Using Minilaparotomy: Do Survival and Complications Vary in Obese?

INTRODUCTION: Peritoneal dialysis catheter (PDC) placement for chronic kidney disease (CKD) amongst overweight and obese patients is difficult owing to deeper operating field. Literature being discordant on survival and complications in this patient subset, we attempted to analyse this research question in Indian population. MATERIALS AND METHODS: We retrospectively analysed PDC inserted by nephrologist using surgical minilaparotomy for survivals and complications amongst 'overweight and obese' cohort ('O') at two tertiary care government hospitals in India, and compared results with normo-weight cohort ('N'), with 12-36 months follow-up. RESULTS: 245 PDCs were inserted by surgical minilaparotomy and 'N' to 'O' ratio was 169:76. 'O' group were more rural residing (P = 0.003) and post-abdominal surgery (P = 0.008) patients. The 1, 2, and 3-year death censored catheter survival rate was 98.6%, 95.8%, and 88.2% respectively in 'O' group, and 97.6%, 94.5% and 91.8% in 'N' group respectively (P = 0.52). Patient survival (P = 0.63), mechanical complications (P = 0.09) and infective complications (P = 0.93) were comparable despite technically challenging surgery in 'O' group. Refractory peritonitis related PDC removal was comparable (P = 0.54). Prior haemodialysis or catheter related blood stream infections or diabetes were non-contributory to results. CONCLUSIONS: Catheter survival and patient survival amongst obese and overweight CAPD patients was non-inferior to normal weight patients. Mechanical, and infective complications were comparable despite technically challenging abdominal terrain in 'O' group. The overall CAPD performance was good amongst obese and overweight.

Is Twice-weekly Maintenance Hemodialysis Justified?

BACKGROUND: The benefits of twice-weekly dialysis at initiation are significant with respect to access longevity, preservation of residual renal function, economic factors, and patient quality of life. It is widely practiced in developing countries due to resource and financial constraints. We present a 3-year follow-up of patients on twice-weekly dialysis and their outcomes. MATERIAL AND METHODS: This was a 3-year observational follow-up study of patients initiated on twice-weekly hemodialysis. Adequacy and basic cost-effective hematological and biochemical parameters were studied monthly. In case of complications, the patient was shifted to thrice-weekly hemodialysis. RESULTS: 88 incident hemodialysis patients were followed up. Total sessions of hemodialysis (HD) studied were 16,406. The mean hemoglobin level was 9.53 g/dl with hyperphosphatemia in 74.88% patients. The mean residual renal function (RRF) at initiation was 5.71 +/- 3.70 ml/min. The mean interdialytic weight gain was 1.91 +/- 1.26 kg with a mean ultrafiltration of 2600 ± 410 ml. The spKt/V and eKt/V were adequate in 68.54% and 48.34% patients; however, the standard Kt/V of 2 was achieved in only 10.51% patients. Emergency HD was done in 41 sessions (0.24%). There were 24 deaths (27.27%) during this period with the mean time to mortality being 503.12 +/- 296.62 days. CONCLUSION: Initiation at twice-weekly schedules for patients on maintenance hemodialysis is a viable option with increments in case of requirement, more so in patients with good urine output and residual renal function. The biochemical and hematological parameters were stable and within KDOQI guidelines and do not worsen with time.

Monoclonal gammopathy of renal significance: Spectrum of diseases and approach to a case.

The occurrence of kidney diseases associated with a monoclonal gammopathy in the absence of symptomatic multiple myeloma is increasingly recognized. When the kidney is involved, the monoclonal etiology of these diseases results in clinical and laboratory features distinct from those of other disease, necessitating the nomenclature monoclonal gammopathy of renal significance (MGRS). The detection of these monoclonal diseases involving the kidney is important since they are poorly responsive to conventional immunosuppression and instead require clone-directed therapy. The new International Kidney and Monoclonal research group consensus definition of MGRS includes all proliferative conditions of B cells and/or plasma cells. Renal lesions due to monoclonal immunoglobulins are quite capable of progression with resulting end-stage renal disease development. Hence, these lesions require therapeutic intervention even if they do not satisfy myeloma criteria or the presence of any myeloma defining event. The spectrum of renal lesions that can be observed in a case of MGRS is wide and mirrors the list that may be seen in a case of any plasma cell neoplasm. This includes Ig light chain, heavy chain, and heavy and light chain amyloidosis; immunotactoid glomerulonephritis (GN); monoclonal immunoglobulin deposition disease including light chain, heavy chain, or heavy and light chain disease; light chain proximal tubulopathy; crystal-storing histiocytosis; proliferative GN with monoclonal immunoglobulin deposits; C3 glomerulopathy with monoclonal gammopathy and cast nephropathy. The initial approach after histological assessment is based on presence or absence of monoclonal immunoglobulin deposits. If monoclonality is evident, it is important to distinguish between conditions with deposition of intact immunoglobulin molecule or light chains only. The treatment of MGRS is directed at the underlying neoplastic B-cell or plasma cell clones.

Plasma cell rich acute rejection: Risk factors, treatment and outcomes.

Plasma cell-rich rejection is a rare and poorly defined entity. Its treatment is not clearly defined and has universally poor prognosis. More data should be published from various transplant centers around the world to identify the treatment that has the best outcomes and to formulate treatment guidelines for these cases. It is a retrospective analysis of kidney biopsies form 2008 to 2018. Four hundred biopsied were screened and 55 were found to have features of rejection and among them, 13 had plasma cell-rich rejection. Data of treatment given and the graft survival outcomes in these cases were retrieved by medical records. One patient had complete recovery, three had graft loss and the remaining nine had permanent decline in glomerular filtration rate. Decrease in immunosuppression and presence of infection are risk factors for plasma cell-rich acute rejection (PCAR). It can be acute cell-mediated rejection (ACR)/antibody-mediated rejection (AMR)/ACR+AMR. Resistant rejection, ACR+AMR, C4d positivity, and severe interstitial inflammation are poor prognostic factors. Overzealous decrease in immunosuppression should not be done. Management of immunosuppression during infection is most critical for the development of PCAR. Bortezomib is emerging as a therapeutic modality for the treatment of PCAR.

Posttransplant lymphoproliferative disorder in renal transplant recipients: Experience from a Tertiary Care Center.

Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal complications arising after solid organ or hematopoietic stem cell transplant. The most crucial factor in pathogenesis of PTLDs is either a primary infection with Epstein-Barr virus or reactivation of its latent state due to immune dysregulation. This complex pathobiology leads to a myriad of clinical manifestations due to uncontrolled lymphoproliferation that may be reactive, polymorphous or monomorphous. We report our experience at a tertiary center of six cases detected over a span of six years. All our patients were proven as high grade B-cell lymphoma on histopathology, which remains the gold standard for diagnosis. Two cases were of primary central nervous system lymphoma, two had disseminated disease, fifth showed allograft involvement, and last case presented with gastrointestinal obstruction. All the patients were managed with reduction of immunosuppression, chemotherapeutic agents, and rituximab. Five patients responded well with a follow-up period of 3-28 months since the time of treatment initiation and had preserved renal function with no episodes of disease recurrence or allograft rejection.

Post Transplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative disorder is an extremely fatal complication arising in transplant recipients as a side effect of immunosuppression. PTLDs are seen after both solid organ and hematopoietic stem cell transplants though the incidence is much higher in the former. Primary Epstein-Barr virus (EBV) infection or reactivation due to a state of immune dysregulation along with intensity of immunosuppression used are of paramount importance in pathogenesis of PTLD. EBV associated PTLDs occur early in the post transplant period whereas late onset lymphomas are usually EBV negative. The uncontrolled B cell proliferation can create a spectrum of histological patterns from nondestructive lesions to destructive polymorphic or more aggressive monomorphic PTLDs. Early detection of seropositivity by serial monitoring in the recipient can prevent PTLD development by starting pre-emptive therapy. The mainstay treatment in established cases remains reduction of immunosuppression. Chemotherapeutic and immunomodulatory agents are added sequentially based on the type of PTLD and based on its response to initial therapy. Despite various treatment options available, the morbidity remains high and achieving state of disease remission without causing graft rejection can be quite challenging. Hence, a better understanding in pathobiology of EBV+ versus EBV- PTLDS may help prevent lymphomagenesis in transplant recipients.

Catastrophic Antiphospholipid Syndrome in Immune Thrombocytopenic Purpura - Beyond Tenuous Concomitance!

Significance of antiphospholipid antibodies in immune thrombocytopenic purpura is debatable and pose a diagnostic and therapeutic dilemma. Catastrophic antiphospholipid syndrome is a rare life-threatening entity, occurring in patients with antiphospholipid syndrome, usually after a triggering event. We describe an adult lady of chronic immune thrombocytopenic purpura (in remission) with antiphospholipid antibodies, who presented with rapidly progressive renal failure and had primary antiphospholipid syndrome nephropathy. The index manuscript titled exemplifies the fact that although the presence of APLA in ITP is known, however, management in the absence of clinical event remains debatable and may carry a future risk of thrombotic event/s mandating close monitoring with a high index of suspicion.

Evaluation of cases of membranoproliferative glomerulonephritis according to newer classification: A retrospective record-based study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) has traditionally been classified on electron microscopy (EM) into different types based on the location of the immune complexes. Sethi et al. subsequently suggested a more relevant etiology-based and clinically useful classification based on immunofluorescence. METHODS: In this retrospective study, 18 diagnosed cases of MPGN over a one-year period for which direct immunofluorescence (DIF) study results were available, were selected. Cases without archived records of immunofluorescence photographs/reports were excluded. Histological diagnosis of MPGN was confirmed and DIF results were analyzed with reference to antibodies to IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. RESULTS: Evaluation of cases revealed 8 males and 10 females with age range from 11 to 66 years. Fifteen cases presented with nephrotic syndrome. On evaluation, 88.89% cases (16/18) were immune complex mediated while two (11.11%) were of complement mediated type of MPGN. Among immune complex-mediated cases, a single case of monoclonal gammopathy associated or light chain mediated MPGN was present. CONCLUSION: The classification described by Sethi et al. is easy to use since it relies on DIF instead of EM which is not readily available. Most of the cases were immune complex mediated whereas incidence of complement mediated MPGN, that is, C3 glomerulopathy was low (11.11%). Application of the new classification allows more relevant categorization of cases based on etiology and without the requirement of EM.

Mycophenolate mofetil or cyclophosphamide in indian patients with lupus nephritis: Which is better? A single-center experience.

Mycophenolate mofetil (MMF) is used extensively for the induction therapy of lupus nephritis (LN) and has even outpaced intravenous (i.v.) cyclophosphamide (CyP) as the initial choice of therapy. There are no studies comparing the response of MMF with standard dose i.v. CyP in Indian patients with LN. We conducted a 24-week prospective, randomized, open-label trial comparing oral MMF with monthly i.v. CyP as induction therapy for active biopsy proven Class III and IV LN. The primary end-point was response to treatment at 24 weeks, and the secondary end-points were complete remission, Systemic Lupus Erythematosus Disease Activity Index scores (SLEDAI) and adverse reactions. Of the 40 patients, 17 were randomized to the MMF group and 23 to the i.v. CyP group. Complete remission was seen in nine (52.94%) patients in the MMF group and 11 (47.82%) in the i.v. CyP group. Partial remission was seen in six (35.30%) in the MMF group and nine (39.13%) in the i.v. CyP group. At six months, the cumulative probability of response was not statistically significant between the two groups (P = 1.000). MMF is comparable to i.v. CyP in the management of LN in Indian patients having an equal safety profile. The dose of MMF required was lower than the conventional doses used in other studies suggesting genetic or environmental factors in the Indian population influencing the metabolism of MMF, which requires further evaluation. The cost of MMF is a limiting factor in its use. The use of i.v. CyP is favorable as the monthly doses ensure compliance and is also cost-effective.

Unconventional strategies in the battle of focal and segmental glomerulosclerosis.

A 24-year-old male presented with classic features of the nephrotic syndrome. An initial renal biopsy revealed minimal change disease and thereafter, a second biopsy showed features of focal and segmental glomerulosclerosis. There was no response to conventional immunosuppression, and the patient had to be given rituximab; in spite of this, he went on to develop end-stage renal disease. He continued to have heavy proteinuria leading to severe hypoalbuminemia, thrombosis, infections, and malnutrition, placing the patient in a life-threatening situation. Bilateral renal ablation with embolization of both kidneys with coiling was done at one setting, which finally resolved the proteinuria in the patient. He then underwent a living-related renal transplant, developing recurrence immediately post-transplant. He was again given rituximab along with tacrolimus, mycophenolate mofetil, and prednisolone. There was no response to rituximab, and the patient underwent plasmapheresis, which leads to complete remission. An arteriovenous fistula was created post-transplant to facilitate regular plasmapheresis.

Adult-onset Still's disease with myocarditis and hemophagocytic lymphohistiocytosis: Rare manifestation with fatal outcome.

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology characterized by fever, evanescent pink salmon rash, arthritis, and multiorgan involvement. Here, we report an unusual manifestation of AOSD in a 40-year-old male who presented to our hospital with pyrexia of unknown origin and rash of 3 weeks duration. All his serological investigations and imaging studies were unremarkable. He was fulfilling clinical and laboratory criteria as per Yamaguchi for AOSD and was managed for the same. Our patient did not respond well to the treatment, had a downhill course, and succumbed to his illness. Autopsy confirmed myocarditis and florid bone marrow reactive hemophagocytosis as the cause of his death.

Evans syndrome and its link with systemic lupus erythematosus.

Evans syndrome is a rare syndrome associated with the presence of autoimmune hemolytic anemia and simultaneous or sequential development of thrombocytopenia. It was first described by Evan and Duane in 1951. It is one of the rare presenting features of autoimmune disorders, especially systemic lupus erythematosus (SLE), and sometimes may even precede the onset of disease. Primary Evans syndrome with no cause is very rare and is seen in children. Here, we describe a case of secondary Evans syndrome with severe hemolytic anemia leading to acute kidney injury and recovery thereafter only to develop lupus nephritis a few months later. This is one of the rare presentations of SLE and there are only anecdotal case reports.

Dual pathology as a cause of proteinuria in the post-transplant period; report of a case.

Proteinuria is common after renal transplantation and affects between 35%-45% of patients during the same year as their transplant. We report a case of dual pathology in the renal allograft as a cause of severe proteinuria. A 38-year-old male presented with end-stage renal disease. He underwent live related renal allograft transplant. His immediate post-transplant period was unremarkable. He developed rise in serum creatinine (2.1 mg/dl) 6 months after transplant and was biopsied. He was diagnosed as a case of acute cellular rejection type Ib with suspicion for antibody mediated rejection. He was treated with methylprednisolone to which he showed a good response with return of serum creatinine to 1.6 mg/dl. Subsequently, he developed a nephrotic range proteinuria 6 months after this episode of rejection. Repeat biopsy was performed. He was diagnosed as a case of immune complex mediated glomerulonephritis (GN) (morphologically consistent with pattern of membranoproliferative glomerulonephritis) with chronic humoral rejection in the form of transplant glomerulopathy (TG). IHC for C4d and immunofluorescence studies were instrumental making the diagnosis. He was treated with steroids and rituximab to which he showed a good response with remission of proteinuria. This case highlights the importance of picking up dual pathology in an allograft biopsy to ensure appropriate therapy. The role of C4d and its correct interpretation is further highlighted, especially with regard to pattern (granular versus linear) and location (glomerular capillaries versus peritubular capillaries).

Oxford classification of IgA nephropathy and C4d deposition; correlation and its implication.

Introduction: IgA nephropathy (IgAN) is well known to be the most common form of primary glomerulonephritis throughout the world. The histopathological changes are wide and varied as brought out by the various classification systems like the Haas and Oxford systems. C4d is a well-known biomarker of the complement cascade and has recently been implicated in certain native renal diseases. We attempted to characterize C4d deposition in IgAN and correlate this with histopathology by the Oxford classification system. Patients and Methods: This retrospective study included renal biopsies of 15 cases of IgAN diagnosed on histopathology and immunofluorescence over a period of 2 years. Demographic parameters of age and sex were reviewed. The Oxford classification system was applied to score the cases and immunohistochemistry for C4d was done on all cases to characterize staining pattern and intensity and was correlated with Oxford classification. Results: On histological examination, the cases showed various combinations of lesions ranging from M0E0S0T0 to M1E1S1T1. C4d deposition was found to be occurring mainly in mesangial location (12/15 cases, 80%). Forty percent cases showed C4d deposition in the glomerular capillary walls in a segmental fashion and 26.67% showed global pattern. Other patterns of deposition were arteriolar (53.33%), in peritubular capillaries (26.67%) and in tubular epithelium (20%). Conclusion: On comparing the various patterns of deposition of C4d with the four variables of the Oxford classification system, we found that segmental and global deposition of C4d correlated best with endocapillary proliferation.