A case of chronic kidney disease patient with rapid deterioration of renal function, hair loss, and spontaneous resolution of facial warts after COVID-19 infection.

Background: Individuals with pre-existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID-19. This report presents the case of a patient with CKD who contracted COVID-19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation: A 60-year-old Chinese man with a decade-long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 µmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney-protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two-month follow-up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion: This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate.

Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

Validation of the European Kidney Function Consortium Equation in Chinese Adult Population: An Equation Standing on the Shoulders of Predecessors.

BACKGROUND: Equations based on serum creatinine (SCr) have been extensively applied to estimate glomerular filtration rate (GFR), but their performance is debatable. In 2021, the European Kidney Function Consortium (EKFC) published one novel SCr-based formula, which combined the feature of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and full age spectrum (FAS) equations, but its potential applications remain unknown. We seek to assess the appropriateness of the three equations in Chinese adults. METHODS: A total of 3,692 participants (median age, 54 years) were included. Reference GFR (rGFR) was measured by the 99mTc-DTPA renal dynamic imaging method. Estimated GFR (eGFR) was calculated by the CKD-EPI, FAS, and EKFC equations. Correlation coefficients and Bland-Altman analysis were adopted to evaluate their validity. The performance was assessed in subgroups according to age, sex, rGFR, and SCr, considering the bias, accuracy, and precision. RESULTS: The average rGFR was 74.2 mL/min/1.73 m2. eGFR by EKFC showed a relatively stronger correlation with rGFR (R = 0.749) and a larger area under the receiver operating characteristic curve (0.902). EKFC was significantly less biased and exhibited the highest P30 in the entire population (bias = 3.61, P30 = 73.3%). It also performed well in all analyzed subgroups, especially in participants with normal or slightly impaired renal function (rGFR≥60 mL/min/1.73 m2), and low SCr. CONCLUSIONS: Compared to the other two SCr-based formulas, EKFC performed better in the Chinese. Thus, it might serve as a good alternative, until a more suitable formula is developed for the Chinese population.

Different equations for estimating age-related changes of glomerular filtration rate in the healthy population.

BACKGROUND: Identifying age-related trend of estimated glomerular filtration rate (eGFR) is necessary to assess whether kidney function is healthily aging. This study aimed to investigate the application of CKD-EPI, FAS, and Xiangya equations for the aging estimation of eGFR in the healthy Chinese individuals. METHODS: A total of 36,911 healthy individuals were enrolled in this study. We grouped every ten years to observe the trend of eGFR with aging and investigated decline rate of it by general linear regression analysis in each age-groups. Agreement between equations was determined by intraclass correlation coefficient (ICC) and Bland-Altman plot. We calculated reference interval in each age-group. We further analyzed above statistical indicators in males and females. RESULTS: The eGFR by CKD-EPI, and Xiangya equation started to decline from the age of 18. Whereas eGFR by FAS equation remained stable under 40 years, then decreased more rapidly. Compared with males, the females had a higher level but a faster decline rate of eGFR with aging. Agreement analysis revealed good agreement between CKD-EPI and FAS equations (ICC 0.818-0.920). Agreement between Xiangya and CKD-EPI or FAS equations was poor to moderate in most of the population under 70 years old (ICC 0.282-0.786), but good in individuals above 70 years (ICC 0.769-0.881). CONCLUSIONS: The trend of eGFR with aging was different by CKD-EPI, FAS, and Xiangya equations in the healthy Chinese. It may be necessary to take these equations- or age-related differences into consideration when assessing kidney function in primary health care and clinical practice.

Comparison of glomerular filtration rate estimating equations in older adults: A systematic review and meta-analysis.

BACKGROUND: Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to assess the accuracy and bias of six commonly used equations, including the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPICr) and its combination with cystatin C (CKD-EPICr-Cys), with the corresponding pair of the Berlin Initiative Study equations (BIS1 and BIS2) and the Full Age Spectrum equations (FASCr and FASCr-Cys). METHODS: PubMed and the Cochrane Library were searched for studies comparing estimated GFR (eGFR) with measured GFR (mGFR). We analyzed the difference in P30 and bias among the six equations and investigated subgroups based on the area (Asian and non-Asian), mean age (60-74 years and ≥75 years), and levels of mean mGFR (<45 mL/min/1.73m2 and ≥45 mL/min/1.73m2). RESULTS: 27 studies with 18,112 participants were included, all reporting P30 and bias. BIS1 and FASCr exhibited significantly higher P30 than CKD-EPICr. While no significant differences were observed between FASCr and BIS1, or among the three combined equations in terms of either P30 or bias. Subgroup analyses revealed FASCr and FASCr-Cys achieved better results in most situations. However, in the subgroup of mGFR<45 mL/min/1.73m2, CKD-EPICr-Cys had relatively higher P30 and significantly smaller bias. CONCLUSIONS: Overall, BIS and FAS provided relatively more accurate estimates of GFR than CKD-EPI in older adults. FASCr and FASCr-Cys may be better suited for various conditions, while CKD-EPICr-Cys would be a better option for older individuals with impaired renal function.

METTL3 alleviates D-gal-induced renal tubular epithelial cellular senescence via promoting miR-181a maturation.

Methyltransferase-like protein 3 (METTL3) mediated N6-Methyladenosine (m6A) modification has been implicated in many physiological and pathological processes. However, its function and mechanism in kidney aging are not entirely clear. Here, we investigated changes in m6A levels of aging kidneys and the role of METTL3 in senescent renal tubular epithelial cells and its potential mechanisms. First, we used the naturally aged mouse model and the D-galactose (D-gal)-induced aged mouse model. Dot blot and m6A RNA methylation quantification showed significantly decreased m6A levels in both models. In addition, we observed that METTL3 was down-regulated in D-gal-induced senescent human renal tubular epithelial cell line (HK-2). METTL3 reduction was associated with senescence-related phenotypes of HK-2 cells. We also found that miR-181a-5p attenuated HK-2 senescence by targeting the NF-κB pathway. Moreover, METTL3 was able to promote the maturation of miR-181a-5p and then inhibited the expression of NF-κB and IL-1α. Taken together, we demonstrate that the METTL3/miR-181a-5p/NF-κB axis counteracts HK-2 senescence. Our results suggest that METTL3 may be a novel biomarker and a potential therapy target for kidney aging.

Thyroid function and age-related decline in kidney function in older Chinese adults: a cross-sectional study.

BACKGROUND: Thyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults. METHODS: A total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using ß value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid. RESULTS: In the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (ß = -0.081) and decreasing FT3 (ß = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10-4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47-4.81 pmol/L, 27.6% for those with FT3 of 4.82-5.20 pmol/L, and 34.9% for those with FT3 of 5.21-6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function. CONCLUSIONS: This study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

A risk scoring system for the decreased glomerular filtration rate in Chinese general population.

OBJECTIVE: The aim of this study was to establish a risk scoring system for the decreased glomerular filtration rate (GFR) in Chinese general population. METHODS: Totally 781 participants who underwent a health checkup in The First Affiliated Hospital of Nanjing Medical University from January to September 2017 were involved in the study. Significant variables chosen by multivariable logistic regression analysis were allocated the integral scores in proportion to its odds ratio (OR), and then the risk of decreased GFR was assessed based on the scores. RESULTS: The people with abnormal homocysteine (Hcy) level (OR: 1.534, 95% confidential interval [CI]: 1.075-2.190, P = .018), males (OR: 2.054, 95%CI: 1.365-3.092, P < .001), and those at the age of 46-52 years (OR: 2.943, 95%CI: 1.546-5.605, P = .001), 52-59 years (OR: 3.664, 95%CI: 1.937-6.931, P < .001) and ≥59 years (OR: 13.452, 95%CI: 7.339-24.657, P < .001) were subjected to GFR reduction. These three variables were allocated the integral scores in proportion to its OR, and four risk categories were divided according to the scores. The prevalence of the decreased GFR in people with low (score 0-4, n = 8), below the average (score 4-6, n = 37), above the average (score 6-13, n = 47), and high risks (score ≥ 13, n = 103) was 5.26%, 16.89%, 22.93% and 50.24%, respectively, and this prevalence raised with the increase of scores (P < .001). CONCLUSIONS: A risk scoring system is developed in this study, which may offer a specific risk stratification for GFR reduction in Chinese general population.

A comparison between 2017 FAS and 2012 CKD-EPI equations: a multi-center validation study in Chinese adult population.

BACKGROUND: The recent guidelines recommend using the estimated glomerular filtration rate (eGFR) to evaluate renal function. There are two reported full-age-spectrum (FAS) equations in 2017, which are based on serum cystatin C concentrations with or without accompanying serum creatinine level (FASCr-Cys or FASCys). We compared the performance and assessed the applicability of the new FAS equation with the 2012 CKD-EPI (CKD-EPICys and CKD-EPICr-Cys) equation in Chinese subjects. METHODS: A total of 1184 patients, mean aged 55.06 year who underwent 99mTc-DTPA GFR measurements (rGFR) from four hospitals were enrolled. The bias (eGFR-rGFR), precision (interquartile range of difference [IQR]), and accuracy (the proportion of eGFR within 30% of rGFR [P30]) of eGFR and rGFR calculated by four equations were compared. RESULTS: Generally, the equation based on the combination of Cys and Scr performed superior to that on the basis of Cys alone, either the CKD-EPICr-Cys or the FASCr-Cys. Detailedly, referred to rGFR (67.33 ml/min/1.73 m2), the CKD-EPICys, CKD-EPICr-Cys, FASCys, and the FASCr-Cys estimated GFR 56.46 ml/min/1.73 m2, 62.79 ml/min/1.73 m2, 56.45 ml/min/1.73 m2, and 61.04 ml/min/1.73 m2, gave ROCAUC0.944, 0.954, 0.943, and 0.953, respectively. Another comparison as to bias, precision, P30, and RMSE with FASCr-Cys were - 2.87 ml/min/1.73 m2, 19.01 ml/min/1.73 m2, 74.16%, and 17.84 ml/min/1.73 m2 showed that FASCr-Cys performed approximately more accurate than other equations, as well as the diagnostic consistency of GFR staging. In the rGFR < 60 ml/min/1.73 m2 subgroup, the FASCr-Cys equation showed the best performance. In older subjects, compared with FASCys, CKD-EPICr-Cys, and CKD-EPICys, the FASCr-Cys equation had relatively less bias (- 8.09 vs. - 9.63, - 7.52, - 11.04, P < 0.05), most precise (15.18 vs. 16.32, 15.22, 16.63), and most accuracy, P30 was statistically different from the other equations, and achieved a ideal value > 70%. CONCLUSION: The performance of the FASCr-Cys equation is better than that of the CKD-EPICr-Cys equation in the Chinese population, particularly in the elderly. Yet, further modification of FAS equations from a large-scale study could be more suitable for the Chinese population, particularly in older people.

Mild cognitive impairment in maintenance hemodialysis patients: a cross-sectional survey and cohort study.

INTRODUCTION: Few studies focused on mild cognitive impairment (MCI) in maintenance hemodialysis (MHD) patients. This study was conducted to survey the prevalence, the potent risk factors of MCI in MHD patients, and further observe the progress of MCI in a period of 6 months. METHODOLOGY: Mini-Mental State Examination, and Montreal Cognitive Assessment were used to assess cognitive condition. MHD patients were enrolled from The First Affiliated Hospital of Nanjing Medical University, who had a stable hemodialysis history for more than 3 months. RESULTS: Sixty-four MHD patients and 54 general subjects were finally included. The average age of both groups was more than 60 years. The prevalence of MCI in the MHD group was significantly higher than that in general population (60.9% vs 29.6%, P<0.05). Spearman correlation analysis indicated that MCI was related to age, comorbidities, education years, uric acid, serum albumin, and blood pressure. The prevalence and severity of MCI in the MHD group remained unchanged during the 6 months (prevalence: 59.5%-66.6%, MoCA scores: 22.9-22.5). CONCLUSION: MHD patients sustain a fairly high prevalence of MCI. Multiple risk factors influence the incidence and progression of MCI in MHD patients. More attention should be paid to this special population.

Evaluation value of neutrophil gelatinase-associated lipocalin for the renal dysfunction of patients with chronic kidney disease: A meta-analysis.

OBJECTIVE: The role of neutrophil gelatinase-associated lipocalin (NGAL) for the evaluation of renal function in chronic kidney disease (CKD) has not yet to be determined. We aimed to perform a meta-analysis exploring the correlation between NGAL and glomerular filtration rate (GFR) in CKD patients, and to further identify factors affecting NGAL's performance. METHODS: Studies dated before November 2017 were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. A total of 28 relevant studies (involving 3082 patients from 17 countries) were included. The second version of the Quality Assessment for Studies of Diagnostic Accuracy demonstrated that no significant bias had influenced the methodological quality of the included studies. RESULTS: Neutrophil gelatinase-associated lipocalin showed a strong negative correlation with measured glomerular filtration rate (mGFR). The pooled correlation coefficient (r) with corresponding 95% confidence intervals for the correlation between serum NGAL (sNGAL) and GFR was -0.48, meanwhile that for urine NGAL (uNGAL) and GFR was -0.34. However, NGAL's performance is different in subgroups restricted by clinical settings, race, sex, age, and staging of renal function. CONCLUSION: Neutrophil gelatinase-associated lipocalin could be a renal function evaluation marker for patients with renal dysfunction in CKD. Compared with uNGAL, there was a significant negative correlation between sNGAL and GFR. The performances of sNGAL and uNGAL were restricted by clinical factors that should be considered in regards to the sampling source selection.

Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials.

The role of serum cystatin C (Scys) for the detection of acute kidney injury (AKI) has not been fully discussed. This meta-analysis was aimed to investigate the overall diagnostic accuracy of Scys for AKI in adults, and further identify factors affecting its performance. Studies before Sept. 2016 were retrieved from PubMed, Embase, Web of Science and the Cochrane Library. A total of 30 prospective cohort studies (involving 4247 adults from 15 countries, 982 patients occurring AKI) were included. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools demonstrated no significant bias had influenced the methodological quality of the included studies. Scys showed a high predictive power for all-cause AKI, that the area under the receiver operating characteristic curve was 0.89. The detailed assessment parameters, such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for Scys were 0.82, 0.82, 4.6, 0.22 and 21, respectively. Although Scys could be slightly influenced by the following factors: settings, AKI diagnostic criteria, ethnicity, determination method, age and gender, these factors above did not reach statistically significance. In conclusion, Scys could be a vital promising marker to screen out AKI.