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1.
Int Urol Nephrol ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498275

RESUMO

Tumor growth is intricately linked to the process of angiogenesis, with a key role played by vascular endothelial growth factor (VEGF) and its associated signaling pathways. Notably, these pathways also play a pivotal "housekeeping" role in renal physiology. Over the past decade, the utilization of VEGF signaling inhibitors has seen a substantial rise in the treatment of diverse solid organ tumors, diabetic retinopathy, age-related macular degeneration, and various ocular diseases. However, this increased use of such agents has led to a higher frequency of encountering renal adverse effects in clinical practice. This review comprehensively addresses the incidence, pathophysiological mechanisms, and current evidence concerning renal adverse events associated with systemic and intravitreal antiangiogenic therapies targeting VEGF-A and its receptors (VEGFR) and their associated signaling pathways. Additionally, we briefly explore strategies for mitigating potential risks linked to the use of these agents and effectively managing various renal adverse events, including but not limited to hypertension, proteinuria, renal dysfunction, and electrolyte imbalances.

2.
J Natl Med Assoc ; 116(1): 33-44, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38195327

RESUMO

Diabetic kidney disease (DKD) is the most devastating complication of diabetes mellitus. Identification of patients at the early stages of progression may reduce the disease burden. The limitation of conventional markers such as serum creatinine and proteinuria intensify the need for novel biomarkers. The traditional paradigm of DKD pathogenesis has expanded to the activation of the immune system and inflammatory pathways. Monocyte chemo-attractant protein-1 (MCP-1) is extensively studied, as a key inflammatory mediator that modulates the development of DKD. Recent evidence supports the diagnostic role of MCP-1 in patients with or without proteinuria in DKD, as well as a significant role in the early prediction and risk stratification of DKD. In this review, we will summarize and update present evidence for MCP-1 for diagnostic ability and predicting the progression of DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Monócitos/metabolismo , Proteinúria/complicações , Biomarcadores/metabolismo , Diagnóstico Precoce , Diabetes Mellitus Tipo 2/complicações
3.
Ir J Med Sci ; 193(2): 1047-1054, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37851330

RESUMO

BACKGROUND: A significant proportion of diabetic kidney disease (DKD) experience a rapid decline in eGFR, leading to end-stage kidney disease (ESKD) within months. This single-centered retrospective cohort study aimed to assess the prevalence, clinical profile, and predictors for rapid progression in type 2 diabetes mellitus (T2DM) patients with DKD. METHOD: Three hundred fifty-nine T2DM patients with DKD between January 2018 and 2022 were included and those with superimposed non-diabetic kidney disease, chronic kidney disease 5, and < 6 months follow-up were excluded. They were classified as rapid and non-rapid progressors based on the annual eGFR decline of > 5 ml/min/1.73 m2/year. The primary outcome analyzed was the progression to ESKD. The secondary outcomes were the onset of microvascular and macrovascular complications and predictors for rapid progression as well as ESKD. RESULTS: In a median follow-up of 3.5 years, 61.3% were rapid progressors (mean eGFR decline of 15.4 ml/1.73m2/year) and 38.7% were non-rapid progressors (mean eGFR decline 1.8 ml/1.73m2/year. Among rapid progressors, 61.4% reached ESKD. Severe proteinuria, the presence of retinopathy, and acute kidney injury (AKI) episodes were strong predictors of rapid progression. Cardiovascular disease and diabetic retinopathy (microvascular complications) were significantly higher among rapid progressors and had a mortality rate of 7.2%. CONCLUSION: The majority of type 2 DKD patients were rapid progressors and two-thirds of them developed ESKD. The prevalence of hypertension, cardiovascular disease, diabetic retinopathy, AKI episodes, and mortality was higher in rapid progressors. Severe proteinuria and diabetic retinopathy were found to be strong predictors for rapid eGFR decline and its progression to ESKD.


Assuntos
Injúria Renal Aguda , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Falência Renal Crônica , Humanos , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações , Doenças Cardiovasculares/complicações , Prevalência , Progressão da Doença , Falência Renal Crônica/etiologia , Falência Renal Crônica/complicações , Proteinúria/etiologia , Proteinúria/complicações
4.
J Nephrol ; 36(8): 2191-2208, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37530940

RESUMO

Hydroxychloroquine is one of the oldest disease-modifying anti-rheumatic drugs in clinical use. The drug interferes with lysosomal activity and antigen presentation, inhibits autophagy, and decreases transcription of pro-inflammatory cytokines. Owing to its immunomodulatory, anti-inflammatory, anti-thrombotic effect, hydroxychloroquine has been an integral part of therapy for systemic lupus erythematosus and lupus nephritis for several decades. The therapeutic versatility of hydroxychloroquine has led to repurposing it for other clinical conditions, with recent studies showing reduction in proteinuria in IgA nephropathy. Research is also underway to investigate the efficacy of hydroxychloroquine in primary membranous nephropathy, Alport's syndrome, systemic vasculitis, anti-GBM disease, acute kidney injury and for cardiovascular risk reduction in chronic kidney disease. Hydroxychloroquine is well-tolerated, inexpensive, and widely available and therefore, should its indications expand in the future, it would certainly be welcomed. However, clinicians should be aware of the risk of irreversible and progressive retinal toxicity and rarely, cardiomyopathy. Monitoring hydroxychloroquine levels in blood appears to be a promising tool to evaluate compliance, individualize the dose and reduce the risk of retinal toxicity, although this is not yet standard clinical practice. In this review, we discuss the existing knowledge regarding the mechanism of action of hydroxychloroquine, its utility in lupus nephritis and other kidney diseases, the main adverse effects and the evidence gaps that need to be addressed in future research. Created with Biorender.com. HCQ, hydroxychloroquine; GBM, glomerular basement membrane; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; TLR, toll-like receptor.


Assuntos
Antirreumáticos , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Nefrologia , Humanos , Hidroxicloroquina/efeitos adversos , Nefrite Lúpica/tratamento farmacológico , Antirreumáticos/efeitos adversos
5.
Trop Med Int Health ; 28(8): 588-600, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37403003

RESUMO

The term chronic kidney disease of unknown aetiology (CKDu) refers to chronic kidney disease (CKD) in the absence of diabetes, long-standing hypertension, glomerulonephritis, obstructive uropathy or other apparent causes. An increasing number of CKDu cases have been reported from Latin America, Sri Lanka, India and others over the last two decades. These regional nephropathies share the following common attributes: (a) they affect low-to-middle income countries with tropical climates, (b) involve predominantly rural agricultural communities, (c) male predilection, (d) absence of significant proteinuria and hypertension, and (e) chronic tubulointerstitial nephritis on kidney biopsy. The current body of literature suggests that CKDu may be caused by heat stress, agrochemicals, contaminated drinking water or heavy metals; however, considerable regional disparities in CKDu research make it difficult to establish a common causal link. In the absence of a definite aetiology, specific preventive and therapeutic interventions are lacking. Improvement of working conditions of farmers and labourers, provision of safe drinking water and changes in agricultural practices are some of the measures that have been implemented; however, there is lack of data to assess their impact on the incidence and progression of CKDu. There is a need for a concerted global effort to address the current knowledge gaps, and to develop effective and sustainable strategies to tackle this devastating disease.


Assuntos
Água Potável , Hipertensão , Insuficiência Renal Crônica , Humanos , Masculino , Saúde Pública , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Exposição Ambiental/efeitos adversos , Doenças Renais Crônicas Idiopáticas , Sri Lanka/epidemiologia , Hipertensão/complicações
6.
Ir J Med Sci ; 192(6): 3109-3115, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37171573

RESUMO

BACKGROUND: Uremic pruritus has an impact on the quality of life and sleep of hemodialysis patients, but the majority of cases go unreported and untreated unless severe, due to a lack of awareness. The purpose of this study is to determine the prevalence, associated factors, and impact on health-related quality of life (HR-QOL) and sleep in hemodialysis patients. METHODOLOGY: A single-center observational study of 3 months wherein 120 adults on maintenance hemodialysis were included. Baseline characteristics, dialysis-related factors, and lab parameters influencing uremic pruritus were recorded. Those with uremic pruritus completed "12-item pruritus severity scale (12-PSS)", "SKINDEX10", and "Itch-MOS" questionnaires to evaluate severity, impact on HR-QOL, and sleep respectively. RESULTS: Sixty seven over one hundred twenty (55.83%) patients had pruritus and majority were mild (40.83%) as per 12-PSS. Those with pruritus (n=67) had a mean age of 56.5±11.3 years, most were males (82%), chronic glomerulonephritis (29.1%) was the commonest cause of end-stage kidney disease, 3 active smokers, and 4 seropositive. 65(97%) patients were on twice-weekly dialysis, 36/67 had <5 years' dialysis vintage and acceptable adequacy. There was no significant association between uremic pruritus and dialysis-related/laboratory parameters. Patients with uremic pruritus demonstrated significantly worse "HR-QOL" (p<0.001) on the "SKINDEX-10", and patients' "Itch-MOS" scores demonstrated a significant decline in sleep quality with increasing pruritus severity (p<0.001). CONCLUSION: The majority of patients on maintenance hemodialysis experience uremic pruritus. None of the clinical characteristics, dialysis-related factors, and laboratory parameters affected uremic pruritus. Uremic pruritus patients had the worst HR-QOL & their sleep quality significantly declined as pruritus severity escalated. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Study approval was obtained from Institutional Research Committee and Institutional Ethical Committee (IEC 642/2021). Clinical Trial Registry of India (CTRI) registration (CTRI/2022/01/039143) was also obtained.


Assuntos
Qualidade de Vida , Diálise Renal , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Prevalência , Diálise Renal/efeitos adversos , Prurido/epidemiologia , Prurido/etiologia , Sono
7.
Int Urol Nephrol ; 55(4): 913-928, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36271990

RESUMO

The global burden of diabetic kidney disease (DKD) is escalating, and it remains as a predominant cause of the end-stage renal disease (ESRD). DKD is associated with increased cardiovascular disease and morbidity in all types of diabetes. Prediction of progression with albuminuria and eGFR is challenging in DKD, especially in non-proteinuric DKD patients. The pathogenesis of DKD is multifactorial characterized by injury to all components of the nephron, whereas albuminuria is an indicator of only glomerular injury. The limits in the diagnostic and prognostic value of urine albumin demonstrate the need for alternative and clinically significant early biomarkers, allowing more targeted and effective diabetic treatment, to reduce the burden of DKD and ESRD. Identification of biomarkers, based on multifactorial pathogenesis of DKD can be the crucial paradigm in the treatment algorithm of DKD patients. This review focuses on the potential biomarkers linked to DKD pathogenesis, particularly with the hope of broadening the diagnostic window to identify patients with different stages of DKD progression.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Diabetes Mellitus Tipo 2/complicações , Albuminúria/complicações , Falência Renal Crônica/complicações , Biomarcadores , Progressão da Doença , Taxa de Filtração Glomerular
8.
J Vasc Access ; 24(5): 957-964, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34844464

RESUMO

BACKGROUND: Traditionally, percutaneous transluminal angioplasty (PTA) is a first-line approach for stenosed dialysis accesses and has been performed through the non-thrombosed vein segment. For thrombosed accesses, thrombectomy (whether open or percutaneous) is a standard approach. The primary objective of our study is to determine the clinical and technical outcomes of the trans-radial approach of PTA among thrombosed dialysis accesses, in terms of safety and feasibility, technical and clinical aspects and factors influencing them, as well as assisted primary patency, secondary patency at 6 and 12 months. METHODS: This is a single-center retrospective study that included 150 patients over 3 years. About 123 patients underwent successful percutaneous balloon angioplasty through the radial access. RESULTS: We report an overall technical and clinical success rate of 82%, assisted primary patency rate of about 90.25% at 3 months, 82.93% at 6 months, 73.18% at 1 year, and secondary patency rate of 94% at 1 year. Twenty-seven patients were referred for surgical revisions/creation of a new fistula for reasons like inability to pass wire (6 patients), unfavorable anatomical variations like aneurysms at the proximal segments (5 patients), inability to cross the fistula (5 patients), and persistent fistula dysfunction with no flow after initial balloon dilatation (11 patients). Three patients had hematoma at the radial access site (2.5%) while two patients had the AV fistula segment rupture and were successfully treated conservatively. CONCLUSION: We conclude that PTA through the trans-radial approach to completely thrombosed hemodialysis accesses is a good alternative to transvenous access and has a very good assisted primary patency and secondary patency at 1 year without major complications.


Assuntos
Angioplastia com Balão , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Trombose , Humanos , Angioplastia com Balão/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Trombose/etiologia , Diálise Renal/efeitos adversos
9.
Saudi J Kidney Dis Transpl ; 34(4): 279-287, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345582

RESUMO

Hyperuricemia is a risk factor for the progression of chronic kidney disease (CKD). We compared febuxostat versus allopurinol in the progression of CKD and hyperuricemia in 101 patients with Stage 3-4 CKD treated with febuxostat or allopurinol for at least 6 months for hyperuricemia (>7 mg/dL) between January 2012 and December 2016. Baseline characteristics, serum uric acid (SUA), serum creatinine, and estimated glomerular filtration rate (eGFR) at entry and 6 months were compared. The primary outcome was the decline in eGFR and the secondary outcomes were reductions in SUA and adverse events. Fifty-four were in the febuxostat group and 47 were in the allopurinol group. The baseline characteristics were comparable except for age. The mean dose of febuxostat and allopurinol was 43.70 ± 14.5 mg and 108.51 ± 40 mg, respectively. After 6 months, the median rate of decline in eGFR was 1.2 mL/min/1.73 m2 (IQR: 1.2, 5.5) in the febuxostat group and 3.1 mL/min/1.73 m2 (0.6, 6.2) in the allopurinol group, but this was not statistically significant (P = 0.136). The mean reduction in SUA was significantly better (P = 0.004) in the febuxostat group (3.9 ± 1.7 mg/dL) compared with the allopurinol group (2.1 ± 1.0 mg/dL). Both drugs had no serious adverse events. Febuxostat was better at reducing hyperuricemia than allopurinol, but there was no significant difference in the progression of CKD. Large randomized trials and long-term follow-up are necessary to see whether febuxostat has a favorable effect on the progression of CKD.


Assuntos
Hiperuricemia , Insuficiência Renal Crônica , Humanos , Febuxostat/efeitos adversos , Alopurinol/efeitos adversos , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Hiperuricemia/tratamento farmacológico , Taxa de Filtração Glomerular , Supressores da Gota/efeitos adversos , Ácido Úrico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento
10.
Indian J Nucl Med ; 38(4): 320-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38390542

RESUMO

Purpose of the Study: The purpose of this study was to assess the association of measured glomerular filtration rate (mGFR) using camera-based method with early transplant outcomes. Methodology: Diethylenetriamine pentaacetate renograms of all voluntary kidney donors between January 2016 and December 2022 at Kasturba Hospital, Manipal, India, were retrieved for the study. Recipients' posttransplant biochemical parameters were collected and compared against donors with scaled mGFR >80 ml/min/1.73 m2 (Group 1) and with mGFR between 60 and 80 ml/min/1.73 m2 (Group 2). Donor-recipient pair age, anthropometric parameters, and their differences were also assessed against the immediate transplant outcome. Posttransplant immediate graft function was assessed by posttransplant nadir serum creatinine, day to achieve nadir serum creatinine, the incidence of slow graft or delayed graft function, and serum creatinine at 1-month posttransplantation. Recipients with serum creatinine of >2.5 mg/dl on posttransplant day 7 were taken as slow graft function. Results: A total of 161 donor-recipient pairs were analyzed in the study. In recipients who showed persistently high serum creatinine posttransplant, older donor age(p < 0.001), higher difference in body mass index among the donor-recipient pair (p= 0.03), and mGFR <80ml/min (p < 0.001) were significantly associated. Slow graft function was significantly more in Group II recipients, with donors having mGFR <80ml/min as compared to Group I with mGFR >80 ml/min (37.3% vs. 10.6%) (P < 0.001). Conclusions: Camera-based mGFR using Gates' formula is a reliable tool to predict inferior graft outcomes in the immediate posttransplant period. Kidneys from donors with mGFR of 60-80 mL/min/1.73 m2 are likely to experience slow graft function in the immediate posttransplant period.

11.
J Glob Infect Dis ; 14(2): 64-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910823

RESUMO

Introduction: Hyponatremia is a frequent finding in hospitalized patients and is associated with poor clinical outcomes. While hyponatremia is known to commonly occur in certain infections, its association with melioidosis has not been studied previously. We studied incidence and impact of hyponatremia on clinical outcomes in melioidosis. Methods: This was a retrospective analysis of a single-center hospital registry of culture-positive patients with melioidosis hospitalized during a 10-year period (January 01, 2010, through January 31, 2021). Hyponatremia was defined as serum sodium of <135 mmol/L, and severe hyponatremia as serum sodium <120 mmol/L. The association of hyponatremia with in-hospital mortality, need for intensive care unit (ICU) stay and mechanical ventilation was studied. Results: Of 201 patients with melioidosis, 169 (84.1%) had hyponatremia, with severe hyponatremia in 35 (17.4%) patients. Older age (adjusted odds ratios [OR] 1.03, 95% confidence intervals [CI]: 1.00-1.06; P = 0.049) and acute kidney injury (AKI) (adjusted OR 3.30, 95% CI: 1.19-9.19; P = 0.02) were independently associated with hyponatremia. Twenty-two patients had been evaluated for cause of hyponatremia and of these, 11 (50%) had syndrome of inappropriate antidiuresis. Severe hyponatremia was associated with in-hospital mortality (adjusted OR 3.75, 95% CI: 1.37-10.27; P = 0.01), need for ICU stay (adjusted OR 7.04, 95% CI: 2.88-17.19; P < 0.001) and mechanical ventilation (adjusted OR 3.99, 95% CI: 1.54-10.32; P = 0.004). Conclusion: Hyponatremia occurs in 84.1% of hospitalized patients with melioidosis. Older age and AKI are associated with a higher incidence of hyponatremia. The presence of severe hyponatremia is an independent predictor of in-hospital mortality, need for mechanical ventilation and ICU stay.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35177924

RESUMO

Chronic kidney disease (CKD) is extremely common all over the world and is strongly linked to cardiovascular disease (CVD). The great majority of CKD patients have hypertension, which raises the risk of cardiovascular disease (CVD), end-stage kidney disease, and mortality. Controlling hypertension in patients with CKD is critical in our clinical practice since it slows the course of the disease and lowers the risk of CVD. As a result, accurate blood pressure (BP) monitoring is crucial for CKD diagnosis and therapy. Three important guidelines on BP thresholds and targets for antihypertensive medication therapy have been published in the recent decade emphasizing the way we measure BP. For both office BP and out-of-office BP measuring techniques, their clinical importance in the management of hypertension has been well defined. Although BP measurement is widely disseminated and routinely performed in most clinical settings, it remains unstandardized, and practitioners frequently fail to follow the basic recommendations to avoid measurement errors. This may lead to misdiagnosis and wrong management of hypertension, especially in CKD patients. Here, we review presently available all BP measuring techniques and their use in clinical practice and the recommendations from various guidelines and research gaps emphasizing CKD patients.

14.
Clin Chim Acta ; 523: 339-347, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34666028

RESUMO

Acute kidney injury (AKI) in liver cirrhosis is associated with poor clinical outcomes including an increased long and short-term mortality. The common type of AKI observed in patients with cirrhosis are prerenal AKI (PRA), hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). Despite the growing knowledge and uniform definition for the diagnosis of AKI, there are several challenges including, early diagnosis and management. Precisely differentiating the type of AKI is critical, as therapies differ significantly. In this review, we summarize AKI in liver cirrhosis, their definition, pathophysiology and deficiencies of using the existing biomarker, serum creatinine. We outline the current clinical evidence on the novel biomarker urinary neutrophil gelatinase-associated lipocalin (uNGAL) and its potential role as a biomarker in the early detection, differentiation and prognostication of AKI. This review also briefly talks about other forthcoming biomarkers which hold promise in the management of AKI in liver cirrhosis.


Assuntos
Injúria Renal Aguda , Injúria Renal Aguda/diagnóstico , Biomarcadores , Humanos , Testes de Função Renal , Lipocalina-2 , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico
15.
Indian J Palliat Care ; 27(Suppl 1): S14-S29, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34188374

RESUMO

Patients with chronic kidney disease (CKD) experience high symptom burden, both physical and psychological, that is underrecognized and undertreated. The high symptom burden significantly impacts the quality of life for patients and their families. This review enumerates the various physical and psychological symptoms that patients with CKD often experience and guides in the management of these symptoms. This review follows the recommended international guidelines and has been tailored to suit the Indian context.

16.
Nephrology (Carlton) ; 26(11): 858-871, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34176194

RESUMO

The therapeutic options for preventing or slowing the progression of chronic kidney disease (CKD) have been thus far limited. While angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are, without a doubt, safe and effective drugs, a significant proportion of patients with CKD still progress to end-stage kidney disease. After decades of negative trials, nephrologists have finally found cause for optimism with the introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists (MRAs). Recent trials such as EMPA-REG OUTCOME and CREDENCE have provided evidence of the renal benefits of SGLT2 inhibitors, which have now found widespread acceptance as first-line agents for diabetic CKD, in addition to ACEi/ARBs. Considering results from the DAPA-CKD study, it is expected that their use will soon be expanded to other causes of albuminuric CKD as well, although confirmation from further trials, such as the EMPA-KIDNEY study is awaited. Likewise, although the role of mineralocorticoid receptor overactivation in CKD progression has been known for decades, it is only now with the FIDELIO-DKD study that we have evidence of benefits of MRAs on hard renal endpoints, specifically in patients with diabetic CKD. While further research is ongoing, given the evidence of synergism between the three drug classes, it is foreseeable that a combination of two or more of these drugs may soon become the standard of care for CKD, regardless of underlying aetiology. This review describes pathophysiologic mechanisms, current evidence and future perspectives on the use of SGLT2 inhibitors and novel MRAs in CKD.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Humanos , Rim/metabolismo , Rim/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Resultado do Tratamento
17.
Physiol Rep ; 9(11): e14866, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34120413

RESUMO

Aquaporin-2 (AQP2) is a homotetrameric water channel responsible for the final water reuptake in the kidney. Disease-causing AQP2 mutations induce nephrogenic diabetes insipidus (NDI), a condition that challenges the bodily water balance by producing large urinary volumes. In this study, we characterize three new AQP2 mutations identified in our lab from NDI patients (A120D, A130V, T179N) along the previously reported A47V variant. Using Xenopus oocytes, we compared the key functional and biochemical features of these mutations against classical recessive (R187C) and dominant (R254Q) forms, and once again found clear functional recovery features (increased protein stability and function) for all mutations under study. This behaviour, attributed to heteromerization to wt-AQP2, challenge the classical model to NDI which often depicts recessive mutations as ill-structured proteins unable to oligomerize. Consequently, we propose a revised model to the cell pathophysiology of AQP2-related NDI which accounts for the functional recovery of recessive AQP2 mutations.


Assuntos
Aquaporina 2/genética , Diabetes Insípido Nefrogênico/genética , Adulto , Animais , Aquaporina 2/metabolismo , Western Blotting , Humanos , Lactente , Masculino , Mutação/genética , Oócitos , Linhagem , Xenopus laevis
18.
Int J Nephrol Renovasc Dis ; 14: 23-31, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603439

RESUMO

PURPOSE: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD. PATIENTS AND METHODS: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 - August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes. RESULTS: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (±4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018-1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58-13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06-11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p<0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR. CONCLUSION: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.

19.
Int J Nephrol Renovasc Dis ; 14: 487-494, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992427

RESUMO

INTRODUCTION: Pulmonary hypertension (PH) is an underestimated cardiovascular consequence and a mortality predictor in patients on hemodialysis (HD). Thus, we studied its prevalence, risk factors, association with inflammation/oxidative stress, and cardiac changes in HD patients. METHODS: This was a single-center cross-sectional observational study conducted at a tertiary care hospital. Patients aged >18 years on hemodialysis for at least three months were included and divided into those with and without PH; patients with secondary causes for PH were excluded. Clinical characteristics, HD-related factors, lab parameters (C-reactive protein and malondialdehyde with thiol assay were used as markers of inflammation and oxidative stress, respectively), and echocardiography details were compared. PH was defined as a mean pulmonary artery pressure of >25 mmHg at rest, and it was further divided as mild (25-40 mmHg), moderate (40-60 mmHg), and severe (>60 mmHg). RESULTS: Of 52 patients, 28 patients had PH (mild 24, moderate 4, and none had severe PH) with prevalence of 54%. No difference was found in clinical characteristics, dialysis-related factors, biochemical parameters including inflammation (C-reactive protein; p=0.76), or oxidative stress (thiol; p=0.36 and MDA; p=0.46) between the groups. When compared to individuals without PH, HD patients with PH exhibited significantly more mitral regurgitation (p=0.002). CONCLUSION: Hemodialysis patients have a high prevalence of PH. PH was significantly associated with the presence of mitral regurgitation on echocardiography. Our study did not find differences in traditional risk factors, HD-related factors, and inflammation/oxidative markers between the groups with and without PH.

20.
Asian J Transfus Sci ; 14(1): 63-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162710

RESUMO

Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is due to the production of antibodies by the donor "passenger" B lymphocytes against recipient's red cells. It is a rare disorder encountered mostly in ABO blood group-mismatched solid organ transplantation. The present case report illustrates the clinical presentation and the mode of management of PLS in a bidirectional ABO-incompatible renal transplantation. A 43-year-old male diagnosed with chronic kidney disease Stage 5-D (diabetic nephropathy) Type-2 hypertension with ischemic heart disease underwent ABO bidirectional-mismatched renal transplantation. The blood group of the patient was B Rh D positive and that of the donor (patient's wife) was A Rh D positive. In the pretransplantation phase, immunoglobulin G anti-A titer was 64 by column agglutination method, which was subsequently brought down to 4 by therapeutic plasma exchange and immunosuppression. Good graft function was established in the posttransplantation phase, but a significant drop in the hemoglobin (Hb) was noted. A fall in Hb, peripheral smear findings suggestive of hemolysis, and direct antiglobulin test positivity along with raised lactate dehydrogenase suggested the diagnosis of PLS; the patient was managed successfully for the same by transfusion of O blood group packed red blood cell transfusion and immunosuppression. PLS is a rare but important cause of immune-mediated hemolytic anemia in ABO-mismatched transplants.

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