Nephrology最新文献

Aim: Efepoetin alfa, a novel long-acting erythropoietin (EPO)-hybrid Fc fusion protein, represents a promising erythropoiesis-stimulating agent (ESA) for addressing anaemia in chronic kidney disease (CKD) patients. This Phase 3 trial was to assess the efficacy and tolerability of subcutaneous efepoetin alfa in comparison to subcutaneous methoxy polyethylene glycol-epoetin beta in stage 3 or 4 CKD patients.

Methods: A randomised, multicentre, open-label Phase 3 trial enrolled 391 CKD stage 3 or stage 4 patients. Subjects underwent a 20-week correction period followed by an 8-week evaluation period. Responders continued treatment for an extra 24-week extension to evaluate long-term safety, maintenance effectiveness, and the longer treatment interval.

Results: In the efepoetin alfa Q2W (every 2 weeks) group, the response rate was 75.6%; while in the methoxy polyethylene glycol-epoetin beta Q2W group, the response rate was 69.3%. The difference in the response rate was 6.3% with 95% CI (confidence interval) -3.1% to 15.5%. The lower limit of the 95% CI was above the prespecified non-inferiority margin of -9.0%. Adverse event rates were comparable between the treatment groups.

Conclusion: Efepoetin alfa demonstrated non-inferiority to methoxy polyethylene glycol-epoetin beta in correcting anaemia and maintaining haemoglobin (Hb) levels among stage 3 and 4 CKD patients. Moreover, the safety profile of efepoetin alfa was comparable to methoxy polyethylene glycol-epoetin beta.

Aim: This study aimed to project the epidemiology of chronic kidney disease (CKD) and its economic impact in Taiwan from 2022 to 2027 using a microsimulation model.

Methods: A virtual representative population of Taiwan was generated using demographic data. The cohort then underwent annual progression using a validated patient-level microsimulation technique, projecting CKD onset and progression based on various factors, including age, sex, eGFR, and urine albumin level. The model also incorporated associated comorbidities like type 2 diabetes mellitus and hypertension and complications such as heart failure, myocardial infarction, and stroke. Healthcare costs associated with diagnosed CKD and kidney replacement therapy (KRT) were also projected.

Results: In 2022, an estimated 10.6% of the total population (2.5 million individuals) in Taiwan were affected by documented or undiagnosed CKD. Without changes in care standards, this prevalence is projected to rise to 12.4% (3.0 million individuals) by 2027, a relative increase of 17.1%. The prevalence of KRT is expected to grow by 7.0% from 2022 to 2027. Complications related to CKD, including heart failure, myocardial infarction, and stroke, are also projected to increase. The annual healthcare costs for diagnosed CKD and KRT are anticipated to rise by 19.7% from TWD $51.96 billion in 2022 to TWD $62.18 billion in 2027.

Conclusion: The projections underscore the escalating burden of CKD in Taiwan, emphasising the need for proactive strategies focusing on early diagnosis, effective management, and public awareness to mitigate the disease's socioeconomic impact.

A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features.

Hypokalemic periodic paralysis is a hereditary or acquired temporary flaccid paralysis of skeletal muscles, affecting proximal musculature more than distal, as a result of hypokalemia. In this report, we describe a unique case of amphetamine-induced hypokalemic periodic paralysis that has only been described twice in the current literature. A 31-year-old male with a history of substance abuse presented with altered mental status and acute tetraparesis after inhalation of methamphetamine. Labs were significant for marked hypokalemia (1.8 mmol/L), elevated creatine kinase and a positive urine drug screen for methamphetamines. Aggressive potassium replacement was initiated, yet the patient remained hypokalemic, with worsening neurological status and aphasia. Intubation and mechanical ventilation became a necessity after the patient developed acute hypercapnic respiratory failure (pCO₂ 103 mmHg, pH 7.02). Our patient then received potassium replacement via multiple routes, including intravenous and orogastric administration. After 15 h, his potassium normalised, and he was successfully extubated the next day, regaining full motor strength. This case highlights the potential for amphetamine-induced hypokalemic periodic paralysis to cause life-threatening diaphragmatic paralysis and respiratory failure. How methamphetamine exactly induces hypokalemic periodic paralysis remains unclear, yet its indirect sympathomimetic effects with subsequent intracellular potassium shifts possibly explain the resultant hypokalemia. Given that methamphetamine use is on the rise, physicians should have a high index of suspicion for amphetamine-induced hypokalemic periodic paralysis in patients presenting with acute paralysis and a substance use history. Rapid recognition, potassium repletion and respiratory monitoring are essential for patient recovery.

The global administration of mRNA vaccines in response to the coronavirus disease 2019 (COVID-19) pandemic has been crucial in mitigating the spread of the virus. While these vaccines are generally safe and effective, there have been occasional reports of rare adverse effects, including new-onset nephropathies. Primary Sjögren's syndrome (pSS), an autoimmune disorder primarily affecting the exocrine glands, can also present with renal involvement, most commonly as tubulointerstitial nephritis (TIN). A 52-year-old female with a history of pSS developed shortness of breath, generalised edema, and oliguria 1 month after receiving her fourth dose of the COVID-19 mRNA vaccine. Initial evaluation revealed bilateral pleural effusion on chest X-ray. Laboratory evaluations revealed rapidly progressive glomerulonephritis (RPGN) and nephrotic syndrome. Renal biopsy findings showed mesangial expansion, focal crescent formation, pronounced tubulointerstitial nephritis, and positive staining for anti-phospholipase A2 receptor (PLA2R). The temporal association, coupled with renal biopsy findings, strongly suggested a vaccine-related trigger, and the diagnosis of new-onset primary membranous nephropathy (MN) following COVID-19 mRNA vaccination was made. The patient was treated with haemodialysis, plasma exchange, corticosteroid pulse therapy, and immunosuppressive agents, resulting in complete remission of proteinuria within 3 months. This case underscores the potential for COVID-19 mRNA vaccines to precipitate primary MN in patients with pre-existing familial autoimmune conditions such as pSS. It also emphasises the importance of recognising vaccine-related renal complications in autoimmune patients and the necessity for close monitoring and prompt intervention to prevent serious complications.

A 3-year-old, male, Japanese patient with a history of seizure clusters was urgently admitted for febrile status epilepticus. Blood tests found metabolic and respiratory acidosis linked to the seizures and poor oral intake along with unexplained hypokalaemia, hypomagnesaemia and elevated corrected bicarbonate. These abnormalities resolved with fluid therapy, and follow-up testing after discharge found no electrolyte or acid-base disturbances. A review of the previous episodes of seizure clusters revealed similar findings, including hypokalaemia and metabolic alkalosis, raising suspicion of Gitelman syndrome (GS), which was later confirmed by genetic testing. The present case demonstrated that some patients with GS may present electrolyte or acid-base abnormalities only on sick days. Whenever a blood test performed for any pathological condition reveals unexplained hypokalaemia and metabolic alkalosis, the possibility of GS should be considered even if the blood test results are normal except on sick days.

In this review, we discuss the pathophysiology and management of acute kidney injury (AKI) in the setting of acute-on-chronic liver failure (ACLF). ACLF is characterised by the occurrence of acute hepatic and/or extrahepatic organ failure, induced by immune dysregulation and systemic inflammation in patients with chronic liver disease. Kidney involvement is common, with AKI occurring in 30% to > 95% of ACLF patients, depending on the definition used. Since there is a lack of kidney biopsy data in these patients, the underlying pathophysiological basis of AKI remains incompletely understood, and systemic inflammation is believed to be the primary driver of organ injury. The management of AKI has been largely extrapolated from studies in decompensated cirrhosis, and there is little data specifically in the ACLF setting. However, available evidence suggests that structural kidney injury is more common in ACLF than in decompensated CLD, and therefore, AKI in ACLF is less likely to respond to volume repletion and vasopressors. Treatment options remain limited for those who are non-responsive to intravenous fluids and vasopressors. Liver transplantation (LT), with or without kidney transplantation, is the definitive treatment for these patients. At present, extracorporeal therapies such as therapeutic plasma exchange and kidney replacement therapies play a supportive role in ACLF as a bridge to LT; however, the optimal timing and dosing remain unclear. While theoretically, extracorporeal therapies have the potential to reverse or halt progression of organ damage in ACLF, there is limited evidence currently.

Glomerular diseases associated with myeloproliferative neoplasms (MPN) are rare, and most often present with proteinuria and kidney impairment. Its natural history is not well described, although it has been associated with poor prognosis in described cases. Here, we present a case of MPN-related focal segmental glomerulosclerosis (FSGS) secondary to primary myelofibrosis (PMF) and describe its progression with transformation of PMF to leukaemia. A 52-year-old gentleman was referred for lower limb swelling on a background of primary myelofibrosis requiring splenectomy 3 months prior. Kidney function was normal, but there was nephrotic-range proteinuria of 3.6 g (normal range, NR < 0.15 g) and mild hypoalbuminaemia of 29 g/L (NR 33-48 g/L). Urine microscopy was bland with no haematuria or pyuria. A kidney biopsy confirmed secondary FSGS with dysmorphic megakaryocytes in the glomerular capillaries, as well as immunohistochemistry demonstrating the presence of megakaryocytes and erythroid precursors in the interstitium, indicating the presence of extramedullary haematopoiesis. No deposits were seen on immunofluorescence or electron microscopy. Despite an initial response to high-dose corticosteroids, a relapse in proteinuria to 10.9 g was seen 5 months after diagnosis. This coincided with leukaemic transformation, which was confirmed on bone marrow biopsy. We describe a case of FSGS secondary to PMF presenting with normal kidney function and nephrotic syndrome. As far as the authors are aware, this is the first case to detail the progression of kidney disease before and after leukaemic transformation. Ongoing follow-up may provide useful insights into the natural history of this infrequent association.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurologic syndrome characterised by headache, confusion, visual changes, seizures, and neuroimaging findings of posterior cerebral white matter oedema. Cytotoxic and immunosuppressive drugs, such as cyclosporine, are known factors associated with PRES and, along with hypertensive encephalopathy and eclampsia, are the most common causes of the syndrome. So far, studies in cyclosporine-associated PRES have not shown an association between serum cyclosporine levels and the onset of neurologic symptoms, whereas many cases seem to be related to hypertension caused by cyclosporine. We report here, a renal-transplant recipient receiving cyclosporine, who developed acute blindness and seizures 3 days after the initiation of voriconazole for pulmonary aspergillosis. The onset of PRES coincided with an acute rise in cyclosporine levels. This case illustrates that the rapid elevation of cyclosporine levels-even in the therapeutic range-may trigger the onset of PRES and clinicians should be extremely careful when introducing drugs that may interfere with cytochrome P450, especially strong P450 inhibitors such as voriconazole, which reduce cyclosporine metabolism.

Aim: Fibrillary glomerulonephritis (FGN) is a rare deposition disease with unclear aetiology. There are limited case series of FGN described in the literature. Here, we describe the clinicopathological characteristics and outcomes of a series of 26 patients with FGN diagnosed at an Australian tertiary centre for renal diseases over a decade.

Method(s): The present study includes 26 patients with biopsy-proven FGN diagnosed between January 2011 and December 2021.

Results: The average age at presentation was 60 years, with a female predominance. The mean creatinine at presentation was 205 μmol/L. Most of the patients had significant proteinuria, with an average 24-h urine protein of 3.76 g. Associated conditions included four patients with autoimmune disease, one patient with malignancy, and two patients with Hepatitis C infection. Serum electrophoresis demonstrated monoclonality in three patients, although immunofluorescence did not reveal clonal restriction on the renal biopsy. Most patients had mesangial expansion, with an increase in mesangial cellularity and variable degrees of capillary wall thickening. An established membranoproliferative pattern was seen in 10 patients. The median follow-up period was 33 months. Three patients received therapy targeted at FGN. End-stage kidney disease developed in 10 patients, with 6 patients dying during the follow-up period, mostly due to additional cardiovascular disease or sepsis.

Conclusion: This case series of FGN demonstrates that a significant proportion of patients progress towards end-stage kidney disease. The mortality is significant although the cause of death is due to additional conditions rather than directly due to FGN.