AA amyloidosis associated with cancers.

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.

Kidney and urinary tract involvement in systemic mastocytosis.

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) such as mesangioproliferative GN, membranous nephropathy and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.

Long-term complications in patients with childhood-onset nephrotic syndrome.

BACKGROUND: Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. METHODS: This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula: see text] 3 consecutive years without immunosuppressive medication to maintain remission. RESULTS: Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. CONCLUSIONS: In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula: see text] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. A higher resolution version of the Graphical abstract is available as Supplementary information.

The environment and kidney health: challenges and opportunities.

The accelerating environmental degradation as a result of modernisation and climate change is an urgent threat to human health. Environment change can impact kidney health in a variety of ways such as water scarcity, global heating and changing biodiversity. Ever increasing industrialization of health care has a large carbon footprint, with dialysis being a major contributor. There have been calls for all stakeholders to adopt a 'one health approach' and develop mitigation and adaptation strategies to combat this challenge. Because of its exquisite sensitivity to various elements of environment change, kidney health can be a risk marker and a therapeutic target for such interventions. In this narrative review, we discuss the various mechanisms through which environmental change is linked to kidney health and the ways that the global kidney health communities can respond to environmental change.

Management of Lupus Nephritis: An Update.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, and lupus nephritis (LN) is associated with increased morbidity and mortality. Renal biopsy is essential and the gold standard to diagnose LN. Extra-glomerular involvement is seen in up to 60% of patients with LN and is associated with poor outcomes. The revised International Society of Nephrology/Renal Pathology Society classification for LN has changed the parameters for activity index scoring, redefined crescent and highlighted the significance of extra-glomerular involvement. Repeat renal biopsy is done for resistant disease or during a flare, usually when atypical features are present or when the baseline biopsy showed non-proliferative histology. Protocol repeat biopsy may prove to be valuable as a monitoring tool in patients with LN. Newer modalities of therapy like multitargeted therapy and biological agents may pave a way for better outcomes with minimal adverse effects to the patients.

Rituximab in treatment of collapsing FSGS-A case series.

BACKGROUND: Collapsing focal segmental glomerulosclerosis (cFSGS) is an aggressive glomerular disease presenting as a nephrotic syndrome that has lower rates of remission with conventional immunosuppressive therapy and rapidly progresses to end-stage-renal-disease (ESRD). We report eight cases of HIV-negative cFSGS treated with rituximab. METHODS: The current report is a retrospective case series of cFSGS treated with rituximab from January 2011 to March 2020, at varying phases of the disease. RESULTS: Eight out of the 70 cFSGS patients received rituximab. The median age of patients was 30 years (IQR 24.25-37.5); five patients were males. The median serum creatinine, mean serum albumin and median 24 hours urinary protein at presentation was 0.9 (IQR 0.66-1.27) mg/dL, 2.95 ± 1.15 g/dL, 4.87 (IQR 1.64-5.75) g/day, respectively. Two patients were steroid-resistant, one steroid and tacrolimus dependent, one steroid and cyclosporine dependent, two steroids and tacrolimus resistant, one steroid, tacrolimus, cyclophosphamide, mycophenolate mofetil resistant and one steroid-resistant and tacrolimus dependent before rituximab therapy. Rituximab was given either as targeted therapy (after an initial dose of 375 mg/m2 ; patients having CD-19 levels >5/µL or >1% at 1 month received additional low-dose [100 mg] of rituximab), or weekly regimen. Five patients received CD-19 targeted rituximab; three received weekly doses of 375 mg/m2 , cumulative doses being 820 ± 228.03 mg, and 1800 ± 721.11 mg, respectively. At the end of median follow-up of 15 months, five (62.5%) patients were in remission (three partial, two complete remissions), two (25%) were resistant to therapy; one (12.5%) progressed to ESRD. CONCLUSION: Rituximab is reasonably safe and achieves/maintains remission in 60% of cFSGS cases.

Second trimester medical abortion in a primigravida with lupus nephritis and rapidly progressive renal failure: challenges and outcome.

In the second trimester, medical abortion is preferred as it is less invasive, and the surgical method carries more risk. There is a paucity of published literature on medical abortion in women with renal failure requiring haemodialysis. We came across a woman who presented with rapidly progressive renal failure at 18 weeks of gestation and required therapeutic abortion. We are reporting the challenges, outcomes, and precautions to be taken while performing a medical abortion in such a case.

Achieving dialysis adequacy: A global perspective.

Dialysis adequacy is conventionally quantified as net urea clearance. Single pool (sp) Kt/Vurea remains the best studied measure of dialysis adequacy globally. Other measures such as fluid status control, anemia correction, and mineral metabolism are monitored variably. Increasing use of hemodiafiltration across Europe and many parts of Japan and Australia is predicated on studies showing better patient survival with middle molecule clearance. Apart from local clinical practice guidelines, the income level and public health policy of a country determine quality of dialysis services. Among developed nations, small solute clearance adequacy targets are achieved with high frequency. In the United States, dialysis adequacy target is met by focussing on high blood flow rates and large dialyzer size, sometimes at the cost of session time. In Japan, Australia, and Germany, session length is given importance. Dialysis adequacy reporting is restricted and inconsistent in developing nations. The Gulf Cooperation Council countries, Russia and Malaysia, respectively, are close to achieving dialysis adequacy target (spKt/Vurea ≥1.2) universally in their dialysis populations. Patient-reported outcomes are typically measured only in developed countries. Patient survival on dialysis, partly linked to dialysis adequacy, varies greatly around the world, with Japan having the best survival rates. Until the development of better markers of dialysis adequacy, universal consistency in reporting of conventional parameters with a focus on patient-reported measures should be endeavored.

Hematopoietic stem cell donor with IgA nephropathy: Challenges and management algorithm.

Donor safety is of prime importance in allogeneic hematopoietic cell transplantation. The Worldwide Network for Blood and Marrow Transplantation (WBMT) standing committee on donor issues has issued a consensus statement regarding suitability criteria for related adult donors. This committee recommends that donors with a history of immune-mediated glomerulonephritis and abnormal urine tests should preferably undergo bone marrow harvest, to avoid the theoretical risk of granulocyte colony-stimulating factor (G-CSF) induced immune flare-up. We discuss here a unique situation where a related donor with a history of IgA nephropathy (IgAN) insisted on a peripheral blood stem cell harvest. We propose a management plan for this situation, which posed challenges about donor suitability.

Rituximab in maintaining remission in adults with podocytopathy.

Rituximab is currently used after the conventional agents have failed in the management of steroid-dependent (SD)/ steroid-resistant (SR) podocytopathies and have a safer toxicity profile. We report 53 adults with podocytopathies who were managed effectively with CD19-targeted rituximab therapy. METHODS: This was a prospective study carried out at a tertiary care centre in India between January 2014 and June 2019. Adults between 16 and 60 years with SD, frequently relapsing (FR), and SR nephrotic syndrome (NS) due to podocytopathy received rituximab in a CD19-targeted approach. PRIMARY OUTCOME: Percentage of patients who were in remission at 6 and 12 months. Secondary outcome: Percentage of patients in remission at the last follow-up, rituximab dose and adverse events of rituximab therapy. RESULTS: Fifty-three adults with SD/FR/SR NS received CD19-targeted rituximab. The median age at the time of first rituximab injection was 30.09 ± 13.21 (16.53) years. At the time of first rituximab infusion, all patients were in remission with steroids and/or calcineurin inhibitors (CNIs). Fifty (94.33%) patients were in remission at the end of 6 and 12 months and the last follow-up (median: 36 months). The mean total dose of rituximab at 1 year was 788.7 ± 128.1 (6 001 100) mg. At last follow-up (median 36 months), 42 (79%) patients did not require any additional CNI or steroids therapy. No serious adverse events to rituximab were noted. CONCLUSION: CD19-targeted rituximab therapy is safe and efficacious in the management of SD/SR adult podocytopathy. Also, rituximab is effective in maintaining remission in treatment naïve adult SD or FR podocytopathy.

The Global Kidney Health Atlas: Burden and Opportunities to Improve Kidney Health Worldwide.

CKD is a growing public health problem. The Global Kidney Health Atlas (GKHA) is an important initiative of the International Society of Nephrology. The GKHA aims to improve the understanding of inter- and intranational variability across the globe, focusing on capacity for kidney care delivery. The GKHA survey was launched in 2017 and then again in 2019, using the same core data, supplemented by information about dialysis access and conservative care. Based on a WHO framework of the 6 building blocks essential for health care, the GKHA assesses capacity in 6 domains: information systems, services delivery, workforce, financing, access to essential medicines, and leadership/governance. In addition, the GKHA assesses the capacity for research in all regions of the world, across all domains (basic, translational, clinical, and health system research). The results of the GKHA have informed policy and been used to enhance advocacy strategies in different regions. In addition, through documentation of the disparities within and between countries and regions, initiatives have been launched to foster change. Since the first survey, there has been an increase in the number of countries which have registries to document the burden of CKD or dialysis. For many, information about the burden of disease is the first step toward addressing care delivery issues, including prevention, delay of progression, and access to services. Worldwide collaboration in the documentation of kidney health and disease is an important step toward the goal of ensuring equitable access to kidney health worldwide.

Persistent CD-19 depletion by rituximab is cost-effective in maintaining remission in calcineurin-inhibitor dependent podocytopathy.

AIM: A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long-term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI-dependent patients. METHODS: This was a prospective observational study conducted from July 2014 to February 2018. Steroid-dependent nephrotic syndrome or steroid-resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD-19 levels were monitored monthly and patients having CD-19 levels >5/µL and/or > 1% received additional low-dose (100 mg) of rituximab. RESULTS: A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well-tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. CONCLUSIONS: CD-19 targeted rituximab is a safe and cost-effective agent in remission maintenance in adults with CNI dependent. Over three-fourths of the patients with CNI-dependent podocytopathy maintain clinical remission with CD-19 targeted rituximab therapy.

Membranous nephropathy with light chain restricted deposits.

The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M-type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow-up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow-up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non-malignant associated MN with monoclonal deposits on IF.

Calcinosis in juvenile dermatomyositis mimicking cold abscess.

We report a case of dystrophic calcification presenting as soft cystic swelling in a patient with juvenile dermatomyositis. A 15-year-old boy with lumbosacral cystic swelling, which was considered a cold abscess clinically, was evaluated for nonresponse to antitubercular therapy. The cystic swelling had liquefied calcium with a well circumscribed calcified wall on imaging, which was subsequently excised.