Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered complement regulation. We report three cases of kidney limited TMA associated with benign paraproteins that had no other detectable cause for the TMA, representing cases of MGRS. Two of the cases are receiving clone directed therapy, and none are receiving eculizumab. We discuss in detail the pathophysiological basis for this possible association. Our approach to therapy involves first ruling out other causes of TMA as well as an underlying B-cell malignancy that would necessitate direct treatment. Otherwise, clone directed therapy should be considered. If refractory to such therapy or the disease is severe and multisystemic, C5 inhibition (eculizumab or ravulizumab) may be indicated as well.

Acute kidney injury associated with COVID-19 infection: a case report

SARS-Cov2 infection is a highly transmissible disease associated with serious pulmonary disease. Renal involvement is frequent and associated with poor prognosis; however, mechanisms of kidney injury are not well established. We present a SARS-Cov2 patient with severe acute kidney injury. Kidney biopsy findings revealed a pattern of acute tubular necrosis with isometric vacuolization of the proximal tubule. The interstitium and glomeruli were normal. Electronic microscopy showed multiple viral-like particles in both the glomeruli and proximal tubule. This case study shows how SARS-Cov 2 infection can result in different kinds of kidney lesion.

Percutaneous Transhepatic Biopsy for Extrahepatic Lesions

Purpose The purpose was to assess the diagnostic accuracy and safety of percutaneous transhepatic biopsy for extrahepatic lesions. Materials and Methods Between January 2008 and December 2019, 26 patients (17 men and 9 women; median age, 60 years) underwent percutaneous transhepatic needle biopsy for extrahepatic lesions at our institution. Transhepatic biopsy was deemed appropriate compared with other biopsy routes or methods (i.e., endoscopic or surgical). The lesions were in the porta hepatis (n = 9), retroperitoneum (n = 6), right adrenal gland (n = 4), right kidney (n = 3), lesser omentum (n = 2), duodenum (n = 1), pleura (n = 1), and inferior vena cava (n = 1). The median maximal diameter of the lesions was 45.5 mm (range, 18–148 mm). Core-needle biopsy was performed in all patients. Eighteen-gauge and 21-G needles were used in 25 and one patient, respectively. Ultrasound was used for biopsy in 21 patients, and CT fluoroscopy was used in five patients. Postbiopsy tract embolization was performed in three patients. Technical success and diagnostic accuracy of the biopsy were evaluated. Complications were recorded using the systemic inflammation response (SIR) criteria. Results The pathological results of biopsy were carcinoma (n = 10), lymphoma (n = 9), and other diagnoses (n = 7). Technical success was obtained in all patients. The accurate diagnosis was achieved in 24 of the 26 patients (92.3%). A major complication, a bladder tamponade, was observed in one patient (3.8%) after biopsy of a right kidney lesion. A hematoma caused by iatrogenic renal injury likely obstructed the bladder outlet. Minor complications were observed in three patients (11.5%). Conclusions Percutaneous transhepatic biopsy for extrahepatic lesions is feasible with acceptable safety.

A histopathological review of nephrectomy specimens with an emphasis on pathological assessment of prognostic indicators in malignant lesions

Introduction and Aim: Various non-neoplastic and neoplastic lesions occur in the kidney. Pathological assessment of gross and microscopic features in nephrectomy specimens is essential for diagnosis and predicts the prognosis in malignant tumours. Materials and Methods: Case records of 46 nephrectomy specimens received between two-year periods were retrieved. Detailed gross and histopathological and immunohistochemical features were studied, and malignant tumours were analysed using CAP protocol. Results: Out of 46 nephrectomy specimens, 17 were non-neoplastic and 29 neoplastic. Males constituted 32 cases and females 14 cases. The commonest non-neoplastic kidney lesion was chronic pyelonephritis with hydronephrosis (29%). The mixed epithelial and stromal tumour was the frequently encountered benign tumour (50%). Renal cell carcinoma was the most common malignant tumour in adults (70%) and Wilms tumour in children (4%). Conclusion: Histopathological examination of nephrectomy specimens helps in diagnosing, staging, and planning the management.

Постгипоксическое поражение почек у детей раннего возраста

The article presents mechanisms of chronic kidney disease development both due to the fetus hypoxia and acute kidney lesion. As a result of hypoxia, babies develop kidney fibrosis and progressing of the chronic kidney disease due to the activation of multiple profibrogenic factors. Thus, all babies with prenatal hypoxia and acute kidney lesion in the postnatal period are automatically included into a risk group for the chronic kidney disease and require dynamic observation of a nephrologist.

A clinical report of Burkitt’s lymphoma

Aim. A clinical analysis of Burkitt’s lymphoma (BL) in a 4 years-old female child.Materials and methods. A retrospective analysis was conducted for the history, disease’s course, laboratory and instrumental diagnosis and treatment in patient B. with BL, 4 years old.Results. A 4-yo patient was diagnosed with BL spread to bone marrow, CNS, lymph nodes, both kidneys and spleen. Leukocytosis in common blood profile. Elevated lactate dehydrogenase (LDH) and C-reactive protein (CRP) in biochemical blood profile. Neck lymphadenopathy, mediastinum in computed tomography (CT). Splenomegaly. Multifocal lesion of both kidneys. Retroperitoneal lymphadenopathy. Positive clinical dynamics (normalisation of body weight) is observed with background therapy, LDH 335 U/L in biochemical blood profile, reduced multifocal kidney lesion and spleen size in CT.Conclusion. A clinical case of Burkitt’s lymphoma is reported affecting the bone marrow, CNS, lymph nodes, both kidneys and spleen. Intensive polychemotherapy allowed stabilisation of the patient and containment of oncological processes.

Nghiên cứu đặc điểm lâm sàng và cận lâm sàng bệnh schonlein-henoch ở trẻ em

Study clinical and subclinical features of Henoch-Schönlein purpura in children Objective: Describe clinical and subclinical characteristics of Henoch-Schönlein purpura in children. Find the relationship between kidney lesion and clinical and subclinical manifestations. Methods: Cross-sectional descriptive study, including 51 children <15 years of age diagnosed with Schonlein-Henoch purpura being treated at Hue Central Hospital and Hue University Hospital from April 2016 - May 2018. Results: 51 children entered the study: Male:Female =1.3:1; mean age 7.5  3.4 years. At onset, purpura was present in all cases, gastrointestinal manifestations in 66.7%, arthritis/arthralgias in 54.9%, , renal lesion in 19.6%. The most frequent laboratory abnormalities were Leukocytosis (WBC >10 x 109/L) in 60,8%, high-erythrocyte sedimentation rate (ESR) in 80.4%, microscopic hematuria in 15.7%, proteinuria in 13.7%. Renal lesion were correlated with age of onset. The age group> 10 years old has 6.1 times more kidney lesion than the group ≤ 10 years (OR: 6.1; 95% CI (1.5-26). Conclusion: Clinical and subclinical findings of Schonlein-Henoch purpura in our study are similar to those in the literature. There is an relationship between the age of onset with kidney lesion. Key words: Henoch-Schönlein purpura, kidney lesion

Influence of angiotensin-converting enzyme inhibitor ramipril on indicators of tubular kidney lesion in patients with chronic glomerulonephritis

To research and deepen the understanding of the links between morphological tubular kidney lesion parameters and serum markers – neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18), in patients with chronic glomerulonephritis (CGN) with saved renal function, as well as to estimate therapeutic correction of identified changes using ACE inhibitor ramipril. The diagnosis of “chronic glomerulonephritis” was verified based on clinical, laboratory and morphological data. Patients were divided into 2 clinical groups: patients with CGN and arterial hypertension (AH) and without AH. We used the data of renal biopsies to analyze the indicators of tubular kidney lesion in patients with CGN. Levels of serum NGAL and IL-18 were measured by means of ELISA kits. Treatment of patients was carried out over 24 weeks using the ACE inhibitor ramipril. The average daily dose of ramipril for the entire treatment period for patients with AH was 12.8±5.6 mg, patients of the second group – without AH, were treated with ramipril at a dose of 2.5 mg. On the basis of rank correlation analysis, we demonstrated that the level of serum NGAL is directly correlated with interstitial fibrosis (r=0.65; p<0.05), serum IL-18 – with dystrophic changes in the epithelium of renal tubules (r=0.81; p<0.05).Conclusion. Serum levels of NGAL and IL-18 are one of the most sensitive markers of tubular kidney lesion and have diagnostic efficiency up to 97%. A 24-week treatment with ACE inhibitor ramipril in patients with CGN with and without AH leads to a decrease in the levels of tubular kidney lesion markers.

Phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with combination ipilimumab/nivolumab for metastatic kidney cancer (CYTOSHRINK).

TPS761 Background: Randomized data from the interferon era demonstrated modest survival benefits of cytoreductive nephrectomy (CN) in patients with advanced renal cell carcinoma (aRCC). Results from SURTIME and CARMENA, conducted in the VEGF-targeted therapy era, have challenged the routine use of upfront CN especially in IMDC intermediate and poor risk patients. Furthermore, the treatment landscape in aRCC now includes first-line combination immunotherapy. Data from the Checkmate-214 trial showed that intermediate/poor risk patients have improved overall survival and objective response rate with ipilimumab and nivolumab (I/N) compared to sunitinib. Stereotactic body radiation therapy (SBRT) provides a convenient method for cytoreduction of the primary kidney lesion and may induce an ‘abscopal effect’, leading to enhanced systemic anti-tumour immune response. We hypothesize that SBRT to the primary kidney mass in aRCC patients will enhance the efficacy of I/N compared to standard of care I/N alone. Methods: This phase II trial randomizes untreated aRCC patients in a 2:1 fashion to I/N plus SBRT (30-40 Gy in 5 fractions) to the primary kidney mass between cycles 1 and 2 (experimental arm, E), versus standard of care I/N alone (standard arm, S). Eligible patients have biopsy-proven aRCC (any histology), IMDC intermediate/poor risk disease, and who decline or are unsuitable for CN. Patients with a primary kidney lesion ≥ 20cm, previous abdominal radiation precluding SBRT, or who have a contraindication to I/N are excluded. The primary objective is to compare the efficacy of I/N plus SBRT versus I/N alone, as determined by the hazard ratio for progression free survival (PFS). Secondary objectives include evaluation of safety, overall survival, objective response rate, and health-related quality of life. Exploratory analyses include blood immune signatures and stool microbiome. Up to 78 patients will be enrolled under the assumption of an improved 12-month PFS from 50% (S) to 75% (E), using a two-sided α=0.1, power=80%, and accounting for loss-to-follow-up and stratification using IMDC criteria 1-2 vs 3-6. Clinical trial information: NCT04090710.