Background/Aims: A recent alert from Spanish health authorities warned of a higher incidence of reported hypersensitivity reactions to hemodialysis membranes with polysulfone, in the 2017 review of ...acute reactions to dialyzers found only published reports in the 21st century on polysulfone and its derivatives. The aim is to assess/evaluate the current incidence and characteristics of hypersensitivity reactions in hemodialysis patients. Methods: A retrospective multicentre study in 9 Spanish hospitals evaluated patients in whom a hypersensitivity reaction required a change in dialyzer membrane. Results: A total of 37 patients out of 1561 (2.37%) had hypersensitivity reactions and clinical, epidemiological and analytical data were available for 33 patients (2.11%). The membranes involved were polysulfone (n=23), polynephron (n=8), polyethersulfone (n=1) and polyacrylonitrile (n=1). This distribution reflected the frequency of use of membranes in the participating dialysis units. The reactions were described as type A in 18 cases and type B in 15 cases. There were no significant differences between the two types in clinical symptoms, the composition of the membrane involved, the method of sterilization, the season, or the time during the session in which they occurred. The most frequent symptom was dyspnea/breathlessness (64% of reactions). Eosinophilia was common (74%). 54% of the reactions occurred within the first 30 minutes of hemodialysis, 64% occurred during the first year of dialysis, and 54% required discontinuation of dialysis session. Cellulose triacetate was used as an alternative dialyzer in 78% of the cases. Conclusion: The incidence of hypersensitivity reactions was in the range found in reports from 20 years ago and is observed associated with synthetic membranes, not just polysulfones. Cellulose triacetate appears to be a good alternative for these patients.
C3 glomerulopathy (C3G) is diagnosed by kidney biopsy, with immunofluorescence showing isolated or dominant C3 staining, indicating hyperactivity of the alternative complement pathway as the key ...driver of glomerular injury. Therefore, the lesion is defined by its complement-mediated pathogenesis as much as its histological pattern. As a bevy of complement-targeting agents are moving through development and clinical trials, we review the evolution in treatment paradigms for C3G. Here we survey the limited efficacy of noncomplement targeting therapy before focusing on the work being done on targeting various components of the complement cascade in aiming to provide disease-specific therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In December 2019, a coronavirus 2019 (COVID-19) outbreak, caused by SARS-CoV-2, took place in Wuhan and was declared a global pandemic in March 2020 by the World Health Organization (WHO). It is a ...prominently respiratory infection, with potential cardiological, hematological, gastrointestinal and renal complications. Acute kidney injury (AKI) is found in 0.5%-25% of hospitalized COVID-19 patients and constitutes a negative prognostic factor. Renal damage mechanisms are not completely clear. We report the clinical evolution of hospitalized COVID-19 patients who presented with AKI requiring attention from the Nephrology team in a tertiary hospital in Madrid, Spain.
This is an observational prospective study including all COVID-19 cases that required hospitalization and Nephrology management from March 6th to May 12th. We collected clinical and analytical data of baseline characteristics, COVID-19 and AKI evolutions.
We analyzed 41 patients with a mean age of 66.8 years (SD 2.1), 90.2% males, and with a history of chronic kidney disease (CKD) in 36.6%. 56.1% of patients presented with sever pneumonia or acute respiratory distress syndrome (ARDS), and 31.7% required intensive care. AKI etiology was prerenal in 61%, acute tubular necrosis in the context of sepsis in 24.4%, glomerular in 7.3% and tubular toxicity in 7.3% of the cases. We reported proteinuria in 88.9% and hematuria in 79.4% of patients. 48.8% of patients required renal replacement therapy (RRT). Median length of stay was 12 days (interquartilic range 9-23) and 22% of the population died. Patients who developed AKI during hospital stay presented with higher C-reactive protein, Lactate dehydrogenase-LDH and d-dimer values, more severe pulmonary damage, more frequent intensive care unit-ICU admission, treatment with lopinavir/ritonavir and biological drugs and RRT requirement.
Hypovolemia and dehydration are a frequent cause of AKI among COVID-19 patients. Those who develop AKI during hospitalization display worse prognostic factors in terms of pulmonary damage, renal damage, and analytical findings. We believe that monitorization of renal markers as well as individualized fluid management can play a key role in AKI prevention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
A refined understanding of the role of complement in the pathogenesis of glomerular and other kidney diseases has, over the past two decades, been matched by the development of novel, ...complement-targeting therapies. As we increasingly recognize the important role that complement activation across all three pathways—classical, lectin and alternative—plays in glomerular lesions both rare (e.g. C3 glomerulopathy) and common (e.g. immunoglobulin A nephropathy), we can identify avenues for precise, targeted approaches to modifying the natural history of these kidney diseases. In this review, we survey the evidence on using complement inhibition from the earliest, small-scale studies focusing on C5-targeting agents to more recent, large, multicenter, randomized trials utilizing complement blockade higher up in the complement pathway at the level of C3. We conclude by examining where the field of complement targeting therapy may be headed in light of these studies.
Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. ...Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.
Abstract
BACKGROUND AND AIMS
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease characterized by the formation of cysts that destroy normal renal ...parenchyma. Tolvaptan (vasopressin antagonist) is the only drug approved today to slow disease progression. To assess the efficacy and tolerability of long-term treatment in patients with ADPKD.
METHOD
Retrospective observational study of ADPKD patients on tolvaptan treatment after its approval in Spain in 2017.
RESULTS
Of the 182 patients with ADPKD in follow-up in our practice, 18% (n = 33) initiated treatment because they met criteria for rapid progression. A total of 60.6% (n = 20) males with age 47.64 ± 8.64 years, a baseline GFR of 65.24 ± 20.14 mL/min and a height-adjusted total kidney volume (TKV) of 1137.45 ± 667.58 mL. A total of 72.7% reached the maximum dose (120 mg) with a mean maximum dose of 108.18 ± 22.42 mg and a mean time to reach it of 5.8 ± 9.3 weeks. A total of 90.9% (n = 33) presented side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Other side effects observed were as follows: hypernatremia 9.1% (n = 3), hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily abandoned treatment after a mean time of 3.01 ± 2.17 months. The reasons for discontinuation were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03 (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. The reason for previous withdrawal was hepatotoxicity (n = 2) and aquaretic effects (n = 2). Therefore, the definitive abandonment of treatment was 27.2%. The mean follow-up time of the patients was 39.85 ± 10.04 months.
CONCLUSION
Long-term use of tolvaptan in patients with ADPKD can be considered safe both from the point of view of renal function and side effects. The aquaretic effects are the most frequent. The aquaretic effects and hepatotoxicity are the main reasons for treatment discontinuation. All cases of hepatotoxicity reverted to normal, thus not being considered a serious effect in our experience.
Abstract
BACKGROUND AND AIMS
Tolvaptan, a vasopressin antagonist, is a drug that acts by slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). Its administration is not ...free of side effects. To assess the long-term safety profile of ADPKD patients treated with tolvaptan.
METHOD
Retrospective observational study was undertaken of ADPKD patients on treatment with tolvaptan.
RESULTS
Of the 182 ADPKD patients under follow-up in our hospital, 18% (n = 33) started treatment. Of these, 60.6% (n = 20) were male, with an age of 47.64 ± 8.64 years, a baseline Fg of 65.24 ± 20.14 mL/min, TKVh of 1137.45 ± 667.58 mL and a mean follow-up time of 39.85 ± 10.04 months. A total of 72.7% reached the maximum dose (120 mg), the mean maximum dose reached being 108.18 ± 22.42 mg. At the time of the study, 100% of the patients had reached the maximum dose, the mean time to reach it being 5.8 ± 9.3 weeks. A total of 90.9% (n = 30) presented with side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Others being hypernatremia in 9.1% (n = 3) and hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily discontinued treatment after 3.01 ± 2.17 months. The reasons were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03% (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. Therefore, the treatment discontinuation rate was 27.2%.
The profile of patients with side effects were mostly male (60%) with mean age of 46 ± 8.65 years and TKVh of 1829.93 ± 1172.83 mL .The maximum dose reached in these patients was 107 ± 23.2 mg with a mean time to reach it of 6.19 ± 9.7 ± weeks.
Patients who had more aquaretic side effects were characterized by better baseline prior to renal function and a greater decrease in GFR throughout follow-up. No differences in TRV variations were observed.
CONCLUSION
Tolvaptan treatment is shown to be safe in the long term. However the patient profile to receive treatment must be considered given that a high percentage present aquaretic effects. Regarding hepatotoxicity, although it is another potentially serious effect to consider, it is easily managed and reversible in our studied sample.
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