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BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27â285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Insuficiencia Renal , Humanos , Tasa de Filtración Glomerular , Riñón , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/etiología , Radar , Enfermedades Raras , Sistema de Registros , Insuficiencia Renal/epidemiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Reino Unido/epidemiología , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
PURPOSE: Acute kidney injury (AKI) associated with COVID-19 is associated with poor prognosis. This study assessed the hitherto uninvestigated impact of COVID-19 on the progression and clinical outcomes of patients with AKI. METHODS: Data from 576 patients with AKI admitted between 13/3/20 and 13/5/20 were studied. Increasingly complex analyses, from logistic regressions to competing-risk and multi-state models, have revealed insights into AKI progression dynamics associated with PCR-confirmed COVID-19 acquisition and death. Meta-analyses of case fatality ratios among patients with AKI were also conducted. RESULTS: The overall case-fatality ratio was 0.33 [95% CI (0.20-0.36)]; higher in COVID-19 positive (COVID+) patients 0.52 [95% CI (0.46-0.58)] than in their negative (COVID-) counterparts 0.16 [95% CI (0.12-0.20)]. In AKI Stage-3 patients, that was 0.71 [95% CI (0.64-0.79)] among COVID+ patients with 45% dead within 14 days and 0.35 [95% CI (0.25-0.44)] in the COVID- group and 28% died within 14 days. Among patients diagnosed with AKI Stage-1 within 24 h, the probability of progression to AKI Stage-3 on day 7 post admission was 0.22 [95% CI (0.17-0.27)] among COVID+ patients, and 0.06 [95% CI (0.03, 0.09)] among those who tested negative. The probability of discharge by day 7 was 0.71 [95% CI (0.66, 0.75)] in COVID- patients, and 0.27 [95% CI (0.21, 0.32)] in COVID+ patients. By day 14, in AKI Stage-3 COVID+ patients, that was 0.35 [95% CI (0.25, 0.44)] with little change by day 10, that is, 0.38 [95% CI (0.29, 0.47)]. CONCLUSION: These results are consistent with either a rapid progression in severity, prolonged hospital care, or high case fatality ratio among AKI Stage-3 patients, significantly exacerbated by COVID-19 infection.
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Lesión Renal Aguda , COVID-19 , Progresión de la Enfermedad , Humanos , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/terapia , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Factores de Riesgo , Pronóstico , Estudios RetrospectivosRESUMEN
The purpose of this retrospective review is to question the validity of the condition 'loin pain haematuria syndrome' (LPHS). We highlight the possibility that most patients regarded as having LPHS have a psychiatric/psychological basis for their symptoms, particularly loin pain. Because of this, and because it recurs despite treatment, the review also questions the use of treatments that are invasive, expensive, and carry considerable morbidity.
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Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR. Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered). We assessed ethnicity and socioeconomic status in the following: (i) prevalent RaDaR patients receiving KRT compared with patients with eligible rare disease diagnoses receiving KRT in the UKRR, (ii) patients recruited to RaDaR compared with all eligible unrecruited patients at 2 renal centers, and (iii) the age-stratified ethnicity distribution of RaDaR patients with autosomal dominant polycystic kidney disease (ADPKD) was compared to that of the English census. Results: We found evidence of disparities in ethnicity and social deprivation in recruitment to RaDaR; however, these were not consistent across comparisons. Compared with either adults recruited to RaDaR or the English population, children recruited to RaDaR were more likely to be of Asian ethnicity (17.3% vs. 7.5%, P-value < 0.0001) and live in more socially deprived areas (30.3% vs. 17.3% in the most deprived Index of Multiple Deprivation (IMD) quintile, P-value < 0.0001). Conclusion: We observed no evidence of systematic biases in recruitment of patients into RaDaR; however, the data provide empirical evidence of negative economic and social consequences (across all ethnicities) experienced by families with children affected by rare kidney diseases.
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Background: Recording large-group lectures is commonplace in higher education, allowing students to access content asynchronously and remotely. With the move towards online learning during the COVID-19 pandemic, recording of small-group teaching sessions has also become increasingly common; however, the educational value of this practice is unknown. Methods: All medical students rotating through the Acute Medicine Department of a large teaching hospital were invited to enrol in the study. Consenting students were recorded for the second half of an online case-based learning (CBL) session. The recording was available for 6 months; viewing patterns were analysed. Students were sent a questionnaire after the session, asking them to reflect on the recorded and unrecorded halves of the session. Findings: Thirty-three students underwent recording in 12 separate groups; 31 students (94%) completed the questionnaire. All 31 respondents (100%) described the session as "useful" or "very useful". Twenty-four respondents (77%) recommended continuing to record small-group sessions and 17 (55%) reported being "likely" or "very likely" to watch the recording. Six respondents (19%) reported a negative impact of being recorded. During 6 months of follow-up, no students returned to view the recording for more than 1 minute. Conclusion: Despite positive feedback for the session and high student demand for ongoing recording, no students viewed the recording for any significant duration. One-fifth of students reported a negative impact of being recorded. The findings from this study do not support routine recording of small-group CBL sessions, even where demand for this may exist. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01837-5.
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Lesión Renal Aguda/diagnóstico , Síntomas del Sistema Urinario Inferior/diagnóstico , Atención Primaria de Salud/métodos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Anciano , Creatinina/sangre , Humanos , Hidronefrosis/diagnóstico por imagen , Hidronefrosis/etiología , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Manejo de Atención al Paciente/normas , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/diagnóstico por imagen , Hiperplasia Prostática/patología , Proteinuria/orina , Resultado del Tratamiento , Ultrasonografía/métodosRESUMEN
Increased expression of the regulatory subunit of HIFs (HIF-1α or HIF-2α) is associated with metabolic adaptation, angiogenesis, and tumor progression. Understanding how HIFs are regulated is of intense interest. Intriguingly, the molecular mechanisms that link mitochondrial function with the HIF-regulated response to hypoxia remain to be unraveled. Here we describe what we believe to be novel functions of the human gene CHCHD4 in this context. We found that CHCHD4 encodes 2 alternatively spliced, differentially expressed isoforms (CHCHD4.1 and CHCHD4.2). CHCHD4.1 is identical to MIA40, the homolog of yeast Mia40, a key component of the mitochondrial disulfide relay system that regulates electron transfer to cytochrome c. Further analysis revealed that CHCHD4 proteins contain an evolutionarily conserved coiled-coil-helix-coiled-coil-helix (CHCH) domain important for mitochondrial localization. Modulation of CHCHD4 protein expression in tumor cells regulated cellular oxygen consumption rate and metabolism. Targeting CHCHD4 expression blocked HIF-1α induction and function in hypoxia and resulted in inhibition of tumor growth and angiogenesis in vivo. Overexpression of CHCHD4 proteins in tumor cells enhanced HIF-1α protein stabilization in hypoxic conditions, an effect insensitive to antioxidant treatment. In human cancers, increased CHCHD4 expression was found to correlate with the hypoxia gene expression signature, increasing tumor grade, and reduced patient survival. Thus, our study identifies a mitochondrial mechanism that is critical for regulating the hypoxic response in tumors.