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Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023
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Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.
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Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.
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Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023
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Introduction: Kidney disease due to COVID-19 has been described with several presentations, both in acute phase and in posterior timing of the infection, and kidney biopsy is important for an ideal management. But the process of adequately perform a biopsy during the pandemic entails risks, as being the exposed and infected by the SARS-CoV-2. Besides of the usual potential complications, such as post-biopsy hemorrhage, that may require admission in an already crowded medical structure. For these reasons, attainment of kidney biopsies was limited to those who without an adequate histopathological diagnosis, were at higher risk of inappropriate management, as well as a pathology secondary to the SARS-CoV-2 could be ignored. The aim of this study is to perform a description of the cases biopsied during the SARS-CoV-2 pandemic, being emphasized those whose indication emerged because of the viral infection. Method(s): Descriptive study of the clinical presentation in addition to histopathological findings of cases requiring kidney biopsy during the period of March 2020 - July 2021. Result(s): A total of 37 cases were collected, with a median age of 40 years (range: 60), 51% males and 73% with known history of hypertension. A 35% of the cases presented nephrotic syndrome;with average proteinuria of 4189.5mg/24h. The most frequent histopathological diagnosis was focal segmental glomerulosclerosis (FSGS), accounting for 40% of the cases. 4 patients required biopsy after COVID-19. One of them presented with Acute Kidney Injury (AKI) during the acute phase of the SARS-COV-2 infection with prolonged hemodialysis requirement;presenting histopathological diagnosis of global and segmental glomerulosclerosis. Another case of AKI during the acute phase of infection and subsequent proteinuria presented global and segmental glomerulosclerosis with collapsing characteristics;while 2 cases due to nephrotic syndrome post-infection, presented histological data of minimal change disease and FSGS with acute tubular injury. Conclusion(s): Regardless of the appearance of a new pathology that affects the kidneys, the incidence of entities such as FSGS persists with greater frequency. However, that does not diminish the importance of performing renal biopsies, since this is an essential tool for management in cases where there is overlap of specific glomerual diseases with COVID-19. No conflict of interestCopyright © 2023
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BACKGROUND: Covid 19 is relatively a new disease with varied presentations which can affect multiple organs including kidney. AKI is quite commonly associated with covid-19 infection. However, a lot of research is still needed in understanding of the pathophysiology associated. AIM OF THE STUDY: To study the histological patterns of covid-associated AKI. METHOD(S): This is a retrospective longitudinal study. 109 patients developing AKI after covid -19 infection have been identified. AKI was defined as per KDIGO criteria. Evaluation of AKI was done with routine analysis, and causes other than covid infection were ruled out. Renal biopsy was done, and core specimens were sent for light microscopy and immunofluorescence. RESULT(S): Patients varied from 2 to 76 years. The duration between Covid infection and AKI ranged from 2 weeks to 6 months. Out of 109 patients, 27 (24.7%) showed acute tubular injury, 26 (23.8) showed ATIN, 11 (10%) showed IRGN, 8 (7%) showed crescentic GN, 4 (3.6%) showed chronic TIN,6 (5.5%) showed TMA, 3 (2.75%) showed Ig A nephropathy and Granulomatous TIN each. FSGS and cast nephropathy were seen in 4 (3.6%) patients each. Lupus nephritis, MCD, and Papillary necrosis were seen in one patient each. Rest of the patients, i.e., 10 (9.1%), showed features of background disease. CONCLUSION(S): AKI followed by covid 19 has a variety of pathologic mechanisms. Studying the patterns and their further follow-up will be beneficial since there is very limited data.
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Introduction: Cirrhosis is associated with renal mesangial IgA deposits thought to be due to reduced Immune complex hepatic clearance but associated rapidly proliferative Glomerulonephritis(RPGN) is uncommon. We present a case of IgA predominant RPGN in a cirrhotic patient. Case Description: 36 y/o M with PMHx of psoriasis, ETOH cirrhosis, strong family h/o FSGS presented with AKI along with nephrotic syndrome & microscopic hematuria. Labs: Serum cr: 4.3 mg/dl, UPCR -13 gm/gm, Una <10, Ucr: 153, CK - 409, INR - 1.2, WBC - 6200/ cucm, hb - 6.8 gm/dl, Sr albumin -1.7 gm/dl Urine microscopy: Multiple dysmorphic rbcs & RBC casts Imaging : Renal US without hydronephrosis, TTE revealed no obvious valvular abnormalities or no intra-cardiac vegetations or thrombus. Significant serologies : negative for HIV, viral hepatitis panel, SPEP with immunofixation, Anti-gbm ANA, Anti-ds dna, anca, ASLO and RF, qunatiferon gold, covid-19, INR -1.2 cryocrit negative. Low complent c4 (17mg/dl) with c3 (94mg/dl). Clinical course : Given Cirrhosis & low urine Na;albumin based volume resusictation & HRS protocol was attempted with no improvement. Urine microscopy findings prompted us to do renal biopsy. Biopsy : LM, 12 glomeruli, 3 globally sclerosed: Diffuse, global endocapillary and mesangial hypercellularity. No crescents or microthrombi Glomerular capillary walls with double contours and fuchsinophilic material within mesangial, subendothelial and epimembranous areas. IF: capillary wall and mesangial immunostaining: Ig-A 3+, IgG: 1+, IgM: 1+, C3: 3+,C1q: trace, kappa: 2+, lambda: 3 + EM: 1 glomerulus : Extensive subendothelial expansion + subendothelial/mesangial immune-type deposits & associated cellular interposition. Intramembranous/subepithelial hump-like deposits. No tubuloreticular inclusions.70% podocyte foot process effacement. Patient diagnosed with Ig A predominant MPGN & was treated with solumedrol x 3 and started on steroid taper along with cellcept and discharged home with improvement in creatinine and proteinuria. Discussion(s): Immune complex glomerular disease in cirrhotic patients can be of varied etiology. Although common, renal IgA deposition in cirrhotic patients are of unclear clinical significance. Larger scale clinicopathological studies are needed to understand the risk factors for development of clinically significant glomerulonephritis in cirrhosis.
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Introduction: With the increase of COVID-19 vaccinations, the development of nephrotic syndrome (NS) after vaccination is one of the new concerns. Most NS cases after vaccination are accompanied by minimal change, while others include focal segmental glomerulosclerosis (FSGS). Although an association between COVID-19 infection and collapsing FSGS has been reported especially in patients with APLO1 risk variants, no cases of childhood collapsing FSGS cases after COVID-19 vaccination have been reported up to now. Case Description: Twelve-year-old Japanese girl had been administered BNT162b2 (Pfizer/BioNTech) vaccine. Soon after that, edema had gradually appeared and 15 days after the injection, she was referred to our hospital because of severe edema. She did not have any past nor family history. Blood examination showed severe hypoalbuminemia (sAlb 1.4 g/dL) without kidney disfunction (eGFR 118.0 mL/min/1.73m2) or hypocomplementemia. Urinalysis showed severe proteinuria (urine protein/Cr 12.8 g/gCr) with hematuria, indicating nephrotic syndrome. Prior to treatment, collapsing FSGS was confirmed by kidney biopsy. Prednisolone (PSL) 60 mg/day was started according to the clinical guidelines for pediatric nephrotic syndrome. She had not achieved the complete remission 28 days after administration of PSL, and cyclosporine and lisinopril treatment was started. In addition, we administered two cycles of methyl prednisolone pulse therapy. Finally, she achieved the complete remission after 2.5 months treatment. Comprehensive genetic testing revealed no variant in genes causing steroid resistant NS or asymptomatic proteinuria. Discussion(s): The new onset of NS after vaccination, including COVID-19 vaccination, has been reported. The actual mechanism has not been clarified yet, but some immunological impact is reported to be associated the onset after the vaccination. Interestingly, this patient showed collapsing FSGS which is common as a secondary FSGS, especially in patients with the APOL1 risk variants suffered viral infection. Collapsing FSGS accompanied by COVID-19 infection had been reported to be associated with interferon activation or VEGF activation. Patients with collapsing FSGS after COVID-19 vaccination may have a common etiology.
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Introduction: The association of collapsing Focal Segmental Glomerulosclerosis (FSGS) and mRNA COVID-19 vaccine has been reported. The APOL1 genotype is present in about 75% of African descendants with FSGS. This increases the rates of FSGS as well as HIV-associated nephropathy. We present a case of African-American male with Human Immunodeficiency Virus (HIV) who developed collapsing FSGS after mRNA covid vaccination. Case Description: A 24-year-old male with history of well-controlled HIV on Biktarvy was referred to nephrology for acute kidney injury (AKI) with nephrotic-range proteinuria. Outpatient workup for nephrotic syndrome was unrevealing. Two months prior to AKI, patient received Moderna mRNA COVID-19 vaccine. Renal function worsened with creatinine of 1.6 mg/dL from 1.3 mg/dL with 6 grams of proteinuria. Renal biopsy was done which revealed collapsing FSGS with 10% interstitial fibrosis and tubular atrophy. This was unlikely due to HIV. Treatment was started with Methylprednisolone, Mycophenolate and Lisinopril. A booster COVID-19 vaccine was not recommended. Discussion(s): Proteinuric renal disease is common in patients with history of HIV, but for a patient with well-controlled HIV, other causes of glomerular diseases must be ruled out. We present this case to consider mRNA COVID-19 vaccine as a potential cause of nephrotic syndrome. Glomerular diseases have been reported in temporal association with Moderna and Pfizer BioNTech vaccines. In a case series of 29 biopsy proven glomerular disease that were documented within 1 month of a covid vaccination, 27 out of 29 cases were new onset glomerular diseases. The most common glomerular disease was IgA nephropathy. This a case of collapsing glomerulopathy in relationship with COVID-19 vaccine. Collapsing FSGS has been commonly reported as a cause of AKI in COVID-19, but in our case, we have a patient with collapsing FSGS in the setting of COVID-19 mRNA vaccination. It is unclear of what mechanism attributed to FSGS, but it is possible to consider an inflammatory response against the spike protein as a 'second hit' phenomenon to susceptible individuals, such as African Americans with APOL-1 risk alleles or HIV. This is a potential adverse effect that must be considered after mRNA covid vaccination.
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Introduction: Rapid and mass SARS-CoV-2 vaccination has been a pivotal strategy to curb the COVID-19 pandemic. The use of developed mRNA vaccines has provided effective protection against COVID-19 infection. However, few cases of immunemediated reactions, such as de novo/relapsing glomerulonephritis (GN) have been reported. Case Description: A 45-year-old man with no PMH presented with progressive worsening lower extremity edema 1 week after receiving the Janssen vaccine (Ad26. COV.2). He was not taking any prescribed or over the counter medications. His physical exam showed BP of 160/90 mmHg and +2 lower extremity edema. Laboratory studies revealed the following: BUN 97 mg/dL, serum creatinine 6.7 mg/dL (baseline 0.8 mg/ dL), serum albumin 1.8 g/dL and 24-hour urine protein of 6.5 g. Serological workup was negative. A kidney biopsy showed focal areas of segmental glomerulosclerosis (FSGS), associated with endocapillary foam cells and epithelial cell capping, predominantly involving the takeoff point of the proximal tubule (fig 1). The areas of segmental sclerosis herniated into the proximal tubule. Immunofluorescence was negative and electron microscopy revealed diffuse epithelial foot process effacement (fig 2). The patient was diagnosed with tip variant of FSGS and started on oral prednisone 80 mg daily. He required initiation of dialysis and has no evidence of renal recovery to date. Discussion(s): New cases and relapses of GN's can present shortly after mRNA COVID-19 vaccination. IgA nephropathy, FSGS and minimal change disease have been reported. The tip variant of FSGS usually presents as a primary podocytopathy and has the best prognosis among the various forms of FSGS due to its high response to steroid therapy and low risk of progression.
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Introduction: With the increase in number of the people receiving COVID-19 vaccination, different adverse effects associated with vaccine are being described. While vocal fold paresis (VFP) after both COVID-19 disease and COVID-19 vaccination has been rarely reported, data on this entity in dialysis population is still lacking. We present a case of VFP in a hemodialysis patient following the administration of Pfizer-BioNTech COVID-19 vaccine. Case Description: 45-year-old West Indian female with DM, HTN and End Stage Kidney Disease 2/2 Focal Segmental Glomerulosclerosis s/p kidney transplant that failed after 16 years (on low dose tacrolimus) requiring to start hemodialysis presented to the ED with complaints of voice hoarseness with dysarthria and throat itching that started ~30- 45 minutes after having received the first dose of Pfizer-BioNTech COVID-19 vaccine. She underwent Fiberoptic Indirect Laryngoscopy that showed widely patent airway with mobile vocal cords bilaterally. Symptoms were thought to be secondary to a reaction to the vaccine vs mild GERD. She received steroids and was discharged home within 24 hours after symptomatic improvement on steroid therapy. Her voice normalized within a week. Six months later, she received the second dose of Pfizer-BioNTech vaccine, ~30 minutes after which again developed dysphonia and dysarthria. This time, she was found to have bilateral VFP with incomplete closure. Steroid therapy was reinitiated and is slowly being tapered. Her dysarthria has improved;however, she continues to have hoarseness of voice even after 9 months of having received 2nd dose of vaccine. She has not received the booster dose of vaccine. Discussion(s): Current guidelines recommend booster doses of COVID-19 vaccine for immunocompromised individuals including those on dialysis. The benefits of vaccination markedly outweigh the risk of very rarely reported development of VFP after vaccination. Further research is needed to determine the prevalence of this complication in dialysis patients and to elucidate the underlying mechanisms leading to it.
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Background: Kidney disease due to COVID-19 has been described with several presentations, both in acute phase and in posterior timing of the infection, and kidney biopsy is important for an ideal management. But the process of adequately perform a biopsy during the pandemic entails risks, as being the exposed and infected by the SARS-CoV-2. Besides of the usual potential complications, such as post-biopsy hemorrhage, that may require admission in an already crowded medical structure. For these reasons, attainment of kidney biopsies was limited to those who without an adequate histopathological diagnosis, were at higher risk of inappropriate management, as well as a pathology secondary to the SARS-CoV-2 could be ignored. The aim of this study is to perform a description of the cases biopsied during the SARS-CoV-2 pandemic, being emphasized those whose indication emerged because of the viral infection. Method(s): Descriptive study of the clinical presentation in addition to histopathological findings of cases requiring kidney biopsy during the period of March 2020 - July 2021. Result(s): A total of 37 cases were collected, with a median age of 40 years (range: 60), 51% males and 73% with known history of hypertension. A 35% of the cases presented nephrotic syndrome;with average proteinuria of 4189.5mg/24h. The most frequent histopathological diagnosis was focal segmental glomerulosclerosis (FSGS), accounting for 40% of the cases. 4 patients required biopsy after COVID-19. One of them presented with Acute Kidney Injury (AKI) during the acute phase of the SARS-COV-2 infection with prolonged hemodialysis requirement;presenting histopathological diagnosis of global and segmental glomerulosclerosis. Another case of AKI during the acute phase of infection and subsequent proteinuria presented global and segmental glomerulosclerosis with collapsing characteristics;while 2 cases due to nephrotic syndrome post-infection, presented histological data of minimal change disease and FSGS with acute tubular injury. Conclusion(s): Regardless of the appearance of a new pathology that affects the kidneys, the incidence of entities such as FSGS persists with greater frequency. However, that does not diminish the importance of performing renal biopsies, since this is an essential tool for management in cases where there is overlap of specific glomerual diseases with COVID-19.
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Purpose: Primary focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation (KT) in 30-50% of recipients with a median time of 1.5 months post- KT. Recurrence is associated with early graft loss in 60% of cases. The aim of this study is to assess the efficacy of pre-emptive therapeutic plasma exchange (TPE) and rituximab for the prevention of FSGS recurrence post-KT. Method(s): This single-center, retrospective study included patients receiving KT for primary FSGS between May 2016 and August 2021. Living-donor KT recipients received three sessions of TPE prior to scheduled transplant. Recipients of both living and deceased donor KT received 3 postoperative sessions of TPE followed by one dose of 375 mg/m2 rituximab with or without intravenous immune globulin (IVIG) 0.5 g/kg. Recipients underwent protocol biopsy at one month to screen for FSGS recurrence. The primary endpoint was a composite for disease recurrence including proteinuria (>=1 g/day) or/and biopsy-proven FSGS within one month. Result(s): 54 patients received KT for FSGS during the study period using the TPE/ rituximab protocol. 5 patients (9%) experienced FSGS recurrence within one month of transplant. A total of 10 patients (19%) were found to have disease recurrence within a year, with median (IQR) time to recurrence of 37 days (27-66). White race and history of hypertension were independent risk factors for recurrence, whereas African American race and diabetes were associated with a reduced risk of recurrence. 31 patients (57%) also received IVIG prior to discharge due to concerns for hypogammaglobulinemia. There were 18 documented infections in 13 patients (24%) within 3 months of transplant. Patients who received IVIG had significantly fewer cases of infection (3 cases: 1 viral and 2 COVID-19) compared to patients who did not receive IVIG (15 cases: 4 bacterial, 9 viral, 1 fungal, and 1 COVID-19), p<0.001. At one year, 9 patients (19%) had biopsy-proven rejection (5 acute cellular rejection, 1 antibody-mediated rejection, and 3 mixed rejection). There were no instances of graft loss or mortality observed at one year. Conclusion(s): The utilization of plasma exchange and rituximab may prevent early disease recurrence of FSGS without significant rates of infection, graft loss, or mortality.
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Purpose: The Coronavirus Disease 2019 (COVID-19) pandemic prompted widespread vaccination for the immunosuppressed population starting in January 2021 with minimal information on safety outcomes. The purpose of this study is to evaluate the relationship between kidney pathological changes and mRNA-based COVID-19 vaccines in three kidney transplant recipients. Method(s): We conducted a single-center retrospective case review of three kidney transplant recipients with biopsy-proven acute rejection or pathological changes after 2-dose COVID-19 mRNA vaccination. Renal function, maintenance immunosuppressant regimens, and pathology slides at baseline and post-rejection are recorded. Possible factors associated with the development of rejection were analyzed. Result(s): All participants were male, two received related-living donor transplants and one received a deceased donor transplant. The mean age was 44.3 years. Average time from 2nd COVID-19 vaccine to confirmed rejection or pathological changes was 33.7 days. Two patients received mRNA-1273 COVID-19 mRNA vaccine and one received the BNT162b2 COVID-19 mRNA vaccine. All three allograft biopsies demonstrated findings consistent with acute active antibody mediated rejection and thrombotic microangiopathy. One allograft biopsy also demonstrated findings consistent with collapsing focal segmental glomerular sclerosis. As of November 26, 2021, there have been over 26 reports of solid organ rejection or failure to the Vaccine Adverse Event Reporting System (VAERS) for the COVID-19 mRNA vaccines highlighting the need for further investigation. Conclusion(s): Immunization with COVID-19 mRNA vaccine has potential to precipitate clinically significant immune response to renal allografts leading to acute allograft rejection, thrombotic microangiopathy, and collapsing focal segmental glomerular sclerosis.
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Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest
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Since the outbreak of SARS-COV-2 (COVID-19) in late 2019, there is a wide variety of renal pathology that is most associated with collapsing focal segmental glomerulosclerosis and acute tubular injury. This case presents a patient with new-onset focal segmental glomerulosclerosis - not otherwise specified (FSGSNOS), in a previously healthy adult after a COVID-19 infection. A 30-year-old Caucasian male with no significant past medical history presented with increasing severe generalized edema for 6 months following COVID-19 infection. The patient was admitted to the hospital with a significant acute kidney injury and hypoalbuminemia. Subsequent kidney biopsy revealed focal segmental glomerulosclerosis (NOS variant) with widespread foot process effacement that strongly supported a primary podocytopathy. Serological work-up was unrevealing: C3/C4, HIV, Hepatitis B and C, UPEP, SPEP, and light chains were negative. COVID-19 anti-nucleocapsid and anti-spike antibodies were positive. The patient was started on high-dose prednisone, RAAS blockade, statin therapy, and diuresis. Outpatient follow-up has revealed significant symptomatic improvement of edema with a return to baseline creatinine with initial interventions. COVID-19 infections have been most closely associated with collapsing focal segmental glomerulosclerosis, termed COVAN (corona virus-associated nephropathy), and acute tubular injury. Although the incidence of a non-collapsing FSGS secondary to COVID -19 infection is much lower than COVAN, FSGS-NOS increases the risk of permanent damage to kidney parenchyma if untreated. At this time, management and outcomes of noncollapsing FSGS associated with COVID-19 are not thoroughly studied. Therefore, we present this case to make physicians aware of a rare association between non-collapsing FSGS and COVID-19, as early recognition and treatment can promote recovery.
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Inheritance of the APOL1 G1 or G2 risk alleles in the homozygous or compound heterozygous state, are associated with a ~7-30X increased risk of development of chronic kidney disease (CKD), and with collapsing glomerulopathies in individuals with viral infections including COVID-19 or HIV. Identification of APOL1 high risk genotypes (HRG) can impact patient treatment, prognosis and kidney donor selection. Approximately 13% of African Americans (AA) have an APOL1 HRG, indicating genetic testing in this population can identify those at-risk for CKD development, leading to appropriate patient counseling and management. Here we sought to understand the clinical presentation and variability among patients with APOL1 HRGs, following the implementation of genetic testing for kidney disease with a broad panel at a Louisiana Nephrology clinic. Clinical genetic testing of patient samples was performed using a >380 kidney gene panel (the RenasightTM test, Natera, Inc.) A retrospective review of clinical data for individuals positive for an APOL1 HRG (G1/G1, G2/G2, G1/G2) was performed. We identified 12 patients that were positive for an APOL1 HRG, with all genotypes represented: G1/G1 (n=8), G1/G2 (n=3), and G2/G2 (n=1). Among this cohort, 100% (12/12) were of AA descent. At the time of testing 91% (11/12) of the patients were diagnosed with CKD or ESRD with proteinuria. Biopsy confirmed focal segmental glomerulosclerosis (FSGS) in two patients and collapsing glomerulopathy in one patient. The most common comorbidities among this cohort were hypertension (9/12) and diabetes mellitus (2/12). Four patients had a history of infection with COVID-19 (n=3) or HIV (n=1), three of whom had renal involvement (acute kidney injury or CKD and proteinuria). Use of a broad kidney gene panel enabled the identification of APOL1 HRGs in individuals for which hypertension or diabetes may have otherwise been attributed as the primary cause of CKD. APOL1 HRGs could also provide context for the renal involvement seen in the patients with COVID-19 or HIV infection. Broad panel genetic testing provides an accessible tool for nephrology clinics to help identify individuals at risk for positivity for an APOL1 HRG, including those of AA descent with hypertensive, proteinuric CKD.
ABSTRACT
The glomerular lesions with COVID-19 are uncommon, but include cases of a collapse type of a focal-segmental glomerulosclerosis, occurring during the active infection. Of interest is the establishment of this glomerular disease as a manifestation of a post-COVID-19 damage, occurring at some point after the illness. The case of an 84-year-old woman with a nephrotic syndrome and elevated serum creatinine is presented. Two months earlier the patient had COVID-19 with a bilateral pneumonia as a complication. During the hospital admission she was in a poor general condition. Blood pressure was 220/100 mm Hg. Expressed swelling around the ankles and feet was seen. From the tests ‒ ESR ‒ 147, CRP ‒ 19, total protein ‒ 48 g/l, albumin ‒ 16 g/l, cholesterol ‒ 11.3 mmol/l, triglycerides ‒ 5.3 mmol/l, creatinine ‒ 362 μmol/l, urea ‒ 19.4 mmol/l. Proteinuria ‒ 19.2 g/24 hours. Urine sediment ‒ 3 leukocytes, 20 erythrocytes. Renal biopsy revealed focal-segmental glomerulosclerosis, collapse type. Treatment with corticosteroids and anticoagulants was performed. The patient’s condition improved ‒ the nephrotic syndrome disappeared, serum creatinine was reduced to upper limit values, arterial hypertension was controlled with small amounts of medication. The occurrence of a renal impairment as a late complication of COVID-19 is a possible result of an infection-related immune dysregulation.
ABSTRACT
Objectives: FSGS is a histologic pattern of glomerular injury with numerous causes, frequently associated with kidney disease progression and kidney failure. We examine the US prevalence of FSGS and the impacts of proteinuria and kidney function decline to end-stage kidney disease (ESKD) on HRU and costs. Methods: Descriptive, retrospective analysis based on Optum® de-identified Market Clarity and proprietary Natural Language Processed (NLP) Data (2007-2020). Inclusion criteria: patients with ≥2 FSGS ICD-10 codes (N0x.1) and/or ≥2 FSGS NLP terms within 180 days and ≥30 days apart without associated negation terms. For patients with available claims data (subset of prevalence cohort), HRU/costs analyses were completed (exclusions: pregnancy, cancer, COVID-19). All costs were normalized/discounted and adjusted to 2020 USD using the Consumer Price Index. Results: Estimated standardized US prevalence of FSGS (2016–2019) is 80.86 per 1,000,000 based on US Census Bureau data. Among 320 patients with proteinuria data in the HRU/cost cohort, 60% and 36% had baseline proteinuria >1.5 or >3.5 g/g, respectively. HRU and costs, all per-patient-per-month (PPPM), increased significantly (p<0.05) with proteinuria levels ˃3.5 g/g;(≤1.5 [n=127] vs ˃1.5–3.5 [n=80] vs ˃3.5 g/g [n=113]: emergency department (ED), 0.13 vs 0.13 vs 0.23;outpatient, 3.03 vs 3.41 vs 6.01;total costs, mean $3,026 vs $4,262 vs $10,227). Advancing chronic kidney disease stage to ESKD (stage I [n=99] vs stage III [n=238] vs ESKD [n=180]: ED, 0.09 vs 0.13 vs 0.33;outpatient, 2.58 vs 3.46 vs 11.11;pharmacy claims, 3.59 vs 4.15 vs 5.00;PPPM total costs, mean $1,895 vs $3,898 vs $12,603) was also associated with significant increases in HRU and costs (p<0.05). Conclusion: For patients with FSGS, worsening proteinuria and progression to ESKD are associated with substantial HRU and costs. Approved therapies for FSGS would improve the lives of patients and reduce substantial burden to the healthcare system.
ABSTRACT
BACKGROUND AND AIMS: Cases of collapsing glomerulopathy in association with COVID-19 infection have been reported worldwide, frequently referred to as COVAN (COVID-19 Associated Nephropathy). Affected patients are almost exclusively of Black ethnicity, likely associated with APOL-1 renal risk variants. There remains a paucity of data on patient outcomes, however, and it is unclear how the natural history of this disease may vary from HIV-associated nephropathy (HIVAN) and other non-viral causes of collapsing FSGS. Here, we present a case series of seven patients with presumed COVAN from a single tertiary UK renal centre;highlighting patient demography, biopsy findings, clinical management and short-term renal outcomes. METHOD: We identified all adult patients presenting to our centre with nephrotic syndrome and a renal biopsy demonstrating collapsing glomerulopathy, in association with a positive COVID-19 PCR swab result. Detailed case note reviews were undertaken using electronic health records to extract data relevant to patient demography, co-morbidities, COVID -19 symptoms, renal biopsy findings, treatment and biochemical parameters, both at the time of presentation and during follow-up at 1, 3, 6 and 12 months respectively (where available). RESULTS: In total, we identified seven patients with presumed COVAN. Three of the seven patients were male, median age was 60 years (range 25-80 years). Six of the seven patients were of Black ethnicity and one patient was of South Asian ethnicity (renal transplant recipient with donor ethnicity unknown). All seven patients had a background of hypertension, 5/7 had known chronic kidney disease (CKD), 5/7 had type 2 diabetes mellitus (T2DM) and 4/7 were obese (BMI > 30). In the vast majority of cases, associated COVID-19 symptoms were mild. All patients had profound nephrotic syndrome at the time of renal biopsy, with median urine ACR 1085 mg/mmol (range 682-1380 mg/mmol) and median serum albumin 15 g/L (range 8-20 g/L). Two of seven patients had mild AKI (stage 1) and 5/7 patients had severe AKI (stage 3), with 3 of these patients receiving acute haemodialysis therapy. Management of glomerulopathy was supportive in all cases, including diuresis and anticoagulation (two patients received a short course of oral dexamethasone for their COVID-19 symptoms). ACE inhibitors/angiotensin receptor blockers were re-introduced in two patients and newly commenced in two further patients during follow-up. At 6 months follow-up, one patient remained dialysis dependant and one patient had ongoing decline in renal function (renal transplant recipient);all other patients achieved at least partial remission, with > 50% reduction in urine ACR and some (but not complete) recovery in renal function (Fig. 1). There were no viral particles identified on direct examination of renal biopsy specimens, but 4/7 biopsies exhibited tubulo-reticular inclusions, suggesting an interferon-driven systemic inflammatory process. CONCLUSION: In this case series of seven COVAN cases from a single tertiary UK centre, we noted that in keeping with reports from North America, Black ethnicity patients were disproportionately affected. Partial remission was achieved in most of our cases with supportive treatment only;however, ongoing monitoring of this cohort is required to better understand longer-term patient outcomes. Testing for APOL-1 gene mutations and molecular testing of biopsy samples for this cohort is also ongoing to facilitate better insights into pathophysiology and risk factors associated with this novel disease. (Figure Presented).