Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

Probing insulin sensitivity in diabetic kidney disease: is there a stronger role for functional imaging?

Clinical and experimental evidence support a cause-effect relationship between altered insulin signaling and development of kidney disease of metabolic and non-metabolic origin. However, the current criteria to measure and/or estimate the insulin resistance (IR) are available as research tool but are very difficult to implement in the clinical practice. Therefore, a better understanding of the key players contributing to IR may lead to the development of new non-invasive tools to assess organ-specific insulin sensitivity (IS). We will therefore first introduce the concept that IR and kidney disease may be causally linked as suggested by clinical and experimental studies. We will then, expand on the potential mechanisms leading to altered renal insulin signaling. After reviewing the limitation of currently available strategies to determine IR, this review article will focus on imaging techniques that could be utilized to determine renal IR and that could be tested to predict kidney disease development and progression.

Sickle Cell Disease and Kidney.

Sickle cell disease causes several kidney manifestations. They include defects in urine concentration, impaired handling of potassium and hydrogen ion, albuminuria, acute kidney injury, and chronic kidney disease to name a few. Glomerular hyperfiltration, tubular hyperfunctioning, endothelial damage from repeated sickling and vaso-occlusive episodes, and iron-induced proinflammatory changes in the glomerular mesangium and tubulointerstitium are some of the mechanisms of kidney damage. Albuminuria is one of the most and common clinical features of kidney disease and progresses with age. Kidney disease in patients with sickle cell is associated with increased mortality. Annual screening for proteinuria starting at age 10 years and limiting the use of nonsteroidal anti-inflammatory agents and the use of angiotensin-converting enzyme inhibitors may help in early detection and delaying the progression of kidney disease. Adequate hydration, angiotensin-converting enzyme inhibitors, and adequate control of sickle cell are the main stay of treatment for albuminuria. The hemoglobin goal for patients with sickle cell nephropathy is lesser (10 g/dL) than that for patients with chronic kidney disease due to other causes given that a higher hemoglobin level increases viscosity and the risk of precipitating vaso-occlusive episodes. A multidisciplinary approach is recommended for managing patients with sickle cell and kidney diseases.

Primary extrahepatic portal vein obstruction in adults: a single center experience.

BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) is a heterogenous disease with regards to etiology, pathogenesis, age, and geographical location. This study analyzed our experience with EHPVO in adults aged >20 years. EHPVO associated with pancreatitis and abdominal lymph node tuberculosis compressing the portal vein was excluded. METHODS: Retrospective analysis of the hospital database from January 2000 to December 2009 was done. All patients with liver disease who are attending our department were also prospectively evaluated with Doppler ultrasound for the portal venous system to study the prevalence of EHPVO. Clinical, biochemical, and imaging findings; work up for thrombophilia; treatment given; and follow up were evaluated. RESULT: In the retrospective analysis, primary EHPVO in adults was seen in 108/10,095 (1 %), and in the prospective analysis, it was seen in 16/2,188 (0.73 %). The main clinical presentations were abdominal pain and variceal bleed. Imaging findings included portal cavernoma, portal biliopathy, gallbladder calculi, collaterals, and ascites. The major causative factors identified were hyperhomocysteinemia, antiphospholipid antibodies, and myeloproliferative disorders, while, in a third of patients, none of these risk factors could be identified. Twelve patients were subjected to surgery, while the remaining patients were managed either by medical, endoscopic, or interventional radiological techniques. More than 2 years of follow up was available in 90 patients; two patients died due to uncontrolled bleeding, seven patients required surgery, seven patients showed deterioration in liver function, and one patient developed hepatocellular carcinoma. In the prospective study, three patients were subjected to surgery, and the others were managed medically. CONCLUSION: Primary EHPVO is an uncommon cause of portal hypertension in adults in India, and its etiological spectrum is comparable to the West.

Diagnostic laparoscopy in the era of modern imaging--retrospective analysis from a single center.

INTRODUCTION: A retrospective analysis of utility and outcomes of diagnostic laparoscopy at our center in the last 5 years was done. MATERIAL AND METHODS: In the last 5 years, we subjected 90 patients to diagnostic laparoscopy (DL) when final diagnosis could not be achieved after all necessary imaging methods and serological, cytological, and microbiological investigations. DL was performed under sedation and local anesthesia, and patients were discharged within 24 h. Video documentation along with guided biopsies/collection of the samples for culture and other tests was performed. RESULTS: The commonest indication was ascites (46/90), followed by diffuse liver disease (15), focal liver disease (9), intraabdominal malignancies (10), and miscellaneous (10). Overall accuracy of DL was 91 %. In 64 % of patients, laparoscopy confirmed the clinical diagnosis, and in 27 % of patients, laparoscopy was useful in correcting the diagnosis. DL was performed in 46 patients with low-serum ascitic fluid albumin gradient ascites and ascites of mixed etiology. DL confirmed the suspected diagnosis in 48 %, corrected in 38 %, and yielded unsuspected diagnosis in 15 % patients. In 6 % of patients, laparoscopy was inconclusive. In three patients, there were extensive intraperitoneal adhesions, and adequate examination was not possible. No serious complications were encountered. Minor complications of pain at the port site, ascitic fluid leakage, and port site infection were seen in three, two, and one patient, respectively. CONCLUSION: DL is useful in patients when diagnosis and extent of the disease were unclear especially in ascites of undetermined etiology.

Portal hypertensive polyps: distinct entity.

INTRODUCTION: Gastric mucosal changes in portal hypertension (PH) are well known, but gastroduodenal polyps in PH are rarely described. AIM: This study aims to estimate prevalence of upper gastrointestinal (GI) polyps in patients with PH of any etiology and to evaluate the role of angiogenesis in portal hypertensive polyps. MATERIAL AND METHODS: This is a retrospective analysis of all patients undergoing upper GI endoscopy to compare the etiology of the polyps in the portal hypertensive group vs. those without PH. The diagnosis of polyps was done using standard histological criteria. Another part of the study consisted of prospective analysis of vascular proliferative marker CD 34 and morphometry in 47 patients. RESULTS: A total of 3,811 upper GI endoscopies were done of which 121 patients (3.2 %) had polyps in upper GI tract. In patients with PH (=631), polyps were noted in 16, portal hypertensive polyps in 9, hyperplastic in 6, and fundic gland polyp in 1. In the patients without PH (n = 3,180), polyps of various etiologies were noted in 105 patients. The prevalence of polyps of all causes was similar in both groups (2.5 % vs. 3.3 %, p = 0.3957). Prevalence of hyperplastic polyps was similar in PH (0.95 %) and non-PH group (1.3 %). On immunohistochemistry, PH polyps and PH gastric mucosa had significantly higher vessel diameter of >50 µm, increased vascular density as compared to non-portal hypertensive polyps (PHP) and normal gastric mucosa. CONCLUSION: PHP are definite identifiable lesion in patients of cirrhosis with PH. PHP are probably related to increased angiogenesis in gastric mucosa.

Budd-Chiari syndrome following laparoscopic cholecystectomy.

Patients with thrombophilic disorder while undergoing intra-abdominal surgery may develop splanchnic vein thrombosis which can have dire consequences. Here we report a case of a 38-year-old female who developed acute Budd-Chiari syndrome after a laparoscopic cholecystectomy. She had polycythemia vera which was not diagnosed before surgery. In this report we want to highlight presurgical evaluation of routine biochemical tests and ultrasonography suggestive of myeloproliferative disorders were missed which led to the Budd-Chiari syndrome. We recommend a meticulous look at the routine evaluation done prior to cholecystectomy is essential.

Portal hypertension and ascites in extramedullary hematopoiesis.

Myeloproliferative diseases (MPD) are clonal stem cell disorders which mainly include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). They are characterized by leucocytosis, thrombocytosis, erythrocytosis, splenomegaly, and bone marrow hypercellularity. This might also result in extramedullary hematopoiesis. Abdominal manifestation has been recognized as a feature of these disorders. Splenomegaly and hepatomegaly are fairly common as opposed to ascites which is rare. The MPDs mainly affect the hepatic circulatory systems. The common hepatic manifestations are Budd-Chiari syndrome (BCS), portal vein thrombosis (PVT), and nodular regenerative hyperplasia. A few other features seen in MPDs are caused by extramedullary hematopoiesis, increased hepatic blood flow, and secondary hemosiderosis from multiple blood transfusions. Portal hypertension is found in up to 7% of patients. We report a case of portal hypertension with ascites in a patient with extramedullary hematopoiesis treated with transjugular intrahepatic portocaval shunt (TIPS).

Management of coagulopathy in patients with decompensated liver cirrhosis.

Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis.