ABSTRACT Waldenstrom’s macroglobulinemia (WM) is an IgM associated lymphoplasmacytic lymphoma and kidney disease is a rare complication. We report a case of a 41-year-old male with a history of WM diagnosed 16 years ago, currently with no indication for treatment. The patient presented with nephrotic syndrome and acute kidney injury, hypertension, and multiple lymphadenopathies. A kidney biopsy was performed, showing minimal change disease with lymphomatous infiltration of B-lymphocytes CD20+. Therapy with bortezomib, dexametahasone and rituximab was started and after 6 months of follow-up he presented progressive recovery of renal function and remission of proteinuria. This case illustrates the importance of screening renal disease in WM patients. A kidney biopsy should be performed in those presenting with otherwise unexplained renal failure and/or nephrotic syndrome.

ABSTRACT Pembrolizumab is an immune checkpoint inhibitor used as a cancer therapy. The incidence of immune related adverse events in patients receiving immune checkpoint inhibitors can be as high as 59%-85. Renal adverse effects are uncommon, but the incidence of kidney toxicity related to pembrolizumab is rising as the use of this agent becomes more frequent. We present an uncommon case of biopsy-proven acute interstitial nephritis secondary to pembrolizumab in a patient with metastatic squamous cell carcinoma at the time of his fourth scheduled cycle. Despite the good initial tumor response, pembrolizumab had to be suspended and the patient started on corticosteroids with an initial good response. On his own initiative, the patient stopped prednisolone early, leading to a rebound acute kidney injury. Pembrolizumab was not reintroduced for the risk of further renal function worsening. His clinical status declined due to the progression of the neoplastic disease, and he was referred for palliative care. This case illustrates the importance of systematizing some key points in the approach to acute interstitial nephritis secondary to pembrolizumab: the role of the differential diagnosis of acute kidney injury in a patient under an immune checkpoint inhibitor, the role of glucocorticoids and the controversy about rechallenging this drug after a related acute interstitial nephritis.

Abstract Background Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Resumo Antecedentes: A doença renal é uma manifestação rara de espondilite anquilosante (EA) e as suas alterações patológicas permanecem pouco descritas. O objetivo deste estudo foi investigar a apresentação clínica e alterações patológicas na biópsia renal de doentes com EA bem como rever e discutir a literatura atual sobre o assunto. Métodos: Estudamos retrospectivamente a apresentação clínica e alterações patológicas renais de 15 doentes caucasianos com EA submetidos a biópsia renal entre Outubro de 1985 e Março de 2021. Resultados: Os doentes eram predominantemente homens (66,7%) com idade mediana no momento da biópsia de 47 anos [IIQ 34 - 62]. A creatinina sérica mediana na apresentação foi de 1,3 mg/dL [IIQ 0,9 - 3] e a maioria dos pacientes apresentava também proteinúria (85,7%) e/ou hematúria (42,8%). A indicação mais comum para biópsia renal foi a síndrome nefrótica (33,3%), seguida de lesão renal aguda ou rapidamente progressiva (20%) e doença renal crónica de etiologia desconhecida (20%). A Nefrite intersticial crónica (NIC) (n=3) e a amiloidose AA (n=3) foram os diagnósticos mais comuns. Outros incluíram nefropatia por IgA (NIgA) (n=2), glomeruloesclerose segmentar focal (n=2), nefropatia membranosa (n=1) e glomerulonefrite membranoproliferativa mediada por imunocomplexos (GNMP-IC) (n=1). Conclusões: Apresentamos uma das maiores séries de doenças renais comprovadas por biópsia em doentes caucasianos com EA. Encontramos uma prevalência de NIgA menor do que a relatada anteriormente em coortes asiáticas. Encontramos uma maior prevalência de NIC e uma prevalência menor de amiloidose AA do que a descrita em séries anteriores de pacientes caucasianos. Também apresentamos o primeiro caso de GNMP-IC associada à EA.

ABSTRACT Renal involvement is a common and severe feature of ANCA-associated vasculitis, leading to end-stage kidney disease and death in a considerable number of patients. One of the challenges of ANCA-associated glomerulonephritis is to establish histological features of prognostic value, in order to identify patients who will benefit of immunosuppression. Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. In 2010, Berden et al (J Am Soc Nephrol. 2010; 21: 1628-36) proposed a histopathologic classification based only on glomerular morphology, which is of prognostic value for short-term and long-term renal outcomes. However, over the last years, the results of several studies using multivariable approaches have suggested that the proposed histopathologic classes alone might not be sufficient to predict renal outcome. In order to refine the prognosis of patients with ANCA-associated vasculitis, in 2018, Brix et al (Kidney Int. 2018;94:1177-88) proposed the Renal Risk Score, based on clinical and pathological parameters. In this review, we discuss the prognostic value of the Histopathologic Classification and the Renal Risk Score and their role in routine clinical practice.

ABSTRACT Renal cortical necrosis (RCN) is a rare cause of acute kidney injury (AKI) in developed countries. Drugs, especially non-steroidal antiinflammatory drugs, (NSAIDs) are very rarely described in the literature to cause cortical necrosis. It is characterized by confluent necrosis of the entire cortex apart from a thin rim of viable tissue in the subcapsular, juxtaglomerular areas, and medulla. Although the pathogenesis of the disease remains unclear, the final common pathway is permanent occlusion of afferent arterioles and interlobular arteries in the cortical vasculature. NSAIDs are widely prescribed in general clinical practice. Despite being readily available, a subset of individuals is susceptible to serious renal toxicity and caution should be exercised when these drugs are used. We present the case of a young adult who presented with renal cortical necrosis with irreversible renal failure. Unfortunately, it occurred as a result of inappropriate use of over-the-counter NSAIDs in the setting of the pandemic outbreak of COVID-19.

ABSTRACT Membranoproliferative glomerulonephritis describes a glomerular-injury pattern common to a heterogeneous group of diseases. Evaluation based on clinical and laboratory presentation and immunofluorescence staining on kidney biopsy allows identification of underlying pathophysiological processes and may facilitate proper diagnosis and treatment. Hypocomplementemic urticarial vasculitis syndrome is a rare autoimmune disease of multi-organ involvement. The diagnosis is based on well-defined clinical and laboratory criteria. The pathophysiology is not completely understood but the presence of anti-C1q antibody seems to be involved. Renal involvement occurs in up to 50% of cases. It can be heterogeneous and can be indistinguishable from lupus nephritis. Serological findings and skin involvement distinguish these two entities. We report the case of a 40-year-old female who presented with urticarial skin lesions, hypocomplementemia and nephrotic syndrome. Kidney biopsy showed membranoproliferative glomerulonephritis with full house immune complex deposits. The diagnosis of hypocomplementemic urticarial vasculitis syndrome was made and the patient was successfully treated with prednisolone and mycophenolate mofetil.

ABSTRACT 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.

Monoclonal gammopathies consist of a broad spectrum of diseases, ranging from asymptomatic monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Multiple myeloma is a malignant plasma cell disorder and accounts for 10% of all hematological malignancies and 1% of all malignancies. Differential diagnosis may be challenging, considering the variety of clinical entities with similar behavior. About 15-20% of MM only secretes monoclonal light chains, called light chain MM, which is associated with poorer outcome. Two intermediate concepts were recently introduced, monoclonal gammopathy of renal significance (MGRS) and a wider concept of monoclonal gammopathy of clinical significance (MGCS). The former behaves as a clonal proliferative disorder with associated nephrotoxicity, but does not have the hematological criteria for MM, while MGCS expands this concept to other organs. A subtype of MGCS is monoclonal immunoglobulin deposition disease, a multisystemic disorder characterized by light or heavy chain deposition of monoclonal immunoglobulin in various organs and encompasses three clinical entities: Light-Chain, Light-and Heavy-Chain, and Heavy-Chain Deposition Disease (LCDD, LHCDD and HCDD, respectively). We describe an unusual case of LCDD in which MM was subsequently considered although the proposed criteria are not met. We demonstrate the variability of clinical-pathological presentation of LCDD, requiring a rapid decision-making, particularly in terms of kidney and survival outcomes.