|Year : 2021 | Volume
| Issue : 1 | Page : 19-26
Risk of chronic kidney disease and end-stage renal disease in patients with psoriasis: A systematic review and meta-analysis of cohort studies
Shang- Feng Yang1, Ting- Hao Chen2, Shin- Hung Tsai3, Pei- En Chen4, Ching- Chi Chi5, Tao- Hsin Tung6
1 Division of Nephrology, Department of Medicine, Cheng Hsin General Hospital; Department of Physiology, Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
2 Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
3 Division of Nephrology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan
4 Institute of Health Policy and Management, National Taiwan University; Taiwan Association of Health Industry Management and Development, Taipei, Taiwan
5 Department of Dermatology, Chang Gung Memorial Hospitals, Linkou; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
6 Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan; Science and Education Department, Maoming People's Hospital, Maoming, Guangdong, China
|Date of Submission||13-Feb-2020|
|Date of Decision||07-Oct-2020|
|Date of Acceptance||15-Oct-2020|
|Date of Web Publication||24-Mar-2021|
Ching- Chi Chi
Department of Dermatology, Chang Gung Memorial Hospitals, Linkou
Prof. Tao- Hsin Tung
Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei; Science and Education Department, Maoming People's Hospital, Maoming, Guangdong
Source of Support: None, Conflict of Interest: None
Background: Previous studies showed a higher risk of renal disease among patients with psoriasis; however, this association has been inconsistent. Objectives: This study aimed to carry out a comparison in the probability from suffering renal diseases—including chronic kidney disease (CKD), end-stage renal disease (ESRD), IgA nephropathy (IgAN), glomerular disease (GD), and those resulting in death caused by other renal diseases—in patients with psoriasis. Methods: The systematic review and meta-analysis was conducted to identify cohort studies with reported hazard ratios (HRs) and a 95% confidence intervals (CIs) for the renal outcomes among patients with psoriasis. The meta-analysis was analyzed with the random-effects modeling and was further stratified by psoriasis severity. Results: Three studies were included. Compared to controls without psoriasis, patients with psoriasis had increased risks of CKD (HR: 1.53; 95% CI: 1.20–1.96) and ESRD (HR: 1.24, 95% CI: 1.06–1.46). The risks of CKD (HR: 1.91, 95% CI: 1.78–2.05) and ESRD (HR: 2.72, 95% CI: 1.71–4.34) were increased in servere psoriasis patients. Due to substantial heterogeneity across enrolled studies (I2 = 95%), the risk of CKD in mild psoriasis was insignificant (HR: 1.14, 95% CI 0.87–1.48). Two studies identified severe psoriasis were related to higher risks of IgAN and GD, whereas one study found that mild psoriasis was associated with an increased risk of death from renal disease. Conclusion: Patients with severe psoriasis have a higher risk of incident CKD, ESRD, and GD. However, we only identified two cohort studies that compared the risk of IgAN and GD in psoriasis patients to general populations. It is difficult to conclude that severe psoriasis was associated with higher risks of IgAN and GD. For mild psoriasis, the association with renal disease was less consistent.
Keywords: chronic kidney disease, end-stage renal disease, meta-analysis, psoriasis
|How to cite this article:|
Yang SF, Chen TH, Tsai SH, Chen PE, Chi CC, Tung TH. Risk of chronic kidney disease and end-stage renal disease in patients with psoriasis: A systematic review and meta-analysis of cohort studies. Dermatol Sin 2021;39:19-26
|How to cite this URL:|
Yang SF, Chen TH, Tsai SH, Chen PE, Chi CC, Tung TH. Risk of chronic kidney disease and end-stage renal disease in patients with psoriasis: A systematic review and meta-analysis of cohort studies. Dermatol Sin [serial online] 2021 [cited 2021 Apr 15];39:19-26. Available from: https://www.dermsinica.org/text.asp?2021/39/1/19/311842
| Introduction|| |
Psoriasis, which is characterized by the development of inflammatory plaques on the skin, affects 0.5%–11.4% of adults. It is a complex immune-mediated disease, in which T lymphocytes and dendritic cells play a central role. The chronic inflammation associated with psoriasis is considered a key element linking the disease with various comorbidities such as arthritis, metabolic syndromes, cardiovascular disease, malignancy, and renal disease.,,,,
Chronic kidney disease (CKD) is usually diagnosed in patients with a glomerular filtration rate < 60 mL/min/1.73 m2, with or without albuminuria, for more than 3 months. CKD is an emerging epidemic that contributes to rapidly increasing morbidity and mortality worldwide. Although CKD prevalence varies by region, ethnicity, and socioeconomic indicators, it affects approximately 11% of persons. CKD is also a well-known risk factor for cardiovascular disease and is the 14th leading cause of death globally. Therefore, patients at increased risk of CKD must be identified and provided appropriate treatment.
Compared to other comorbidities, the relationship between psoriasis and renal disease is less well defined. Previous cross-sectional studies have identified an increased prevalence of microalbuminuria and renal failure among patients with psoriasis.,,, Although contradictory results have been shown in patients with mild psoriasis, several population-based cohort studies have demonstrated an association between psoriasis and CKD, end-stage renal disease (ESRD), and glomerular diseases (GDs).,,, Not all of these studies have reached the same conclusions. Some retrospective studies show no difference in renal impairment between patients with psoriasis and the general population or other control groups., Therefore, we conducted a systematic review and meta-analysis to assess the risk of renal disease among patients with psoriasis and to further define risk estimates for patients with mild and severe psoriasis.
| Materials and Methods|| |
Literature search and search strategy
To identify relevant studies, the search strategy “(psoriasis) AND (CKD OR kidney disease OR renal disease OR ESRD OR renal failure OR glomerulonephritis OR uremia OR death from renal disease)” with no language limitations was used to search the Cochrane Library and PubMed from their inceptions to July 15, 2017.
To be included, studies had to meet several criteria: (i) use of a cohort design; (ii) inclusion of a group of people with psoriasis and a group of control patients who did not have psoriasis; (iii) outcomes of CKD, ESRD, IgA nephropathy (IgAN), GD, and death from the renal disease were assessed; and (iv) hazard ratios (HRs) with 95% confidence intervals (CIs) were reported for outcomes related to psoriasis. Two authors independently selected relevant studies; a third author provided arbitration. The full text of all potentially eligible studies was examined to determine whether they met inclusion criteria.
Two authors independently extracted data related to first author, publication year, country, study duration, inclusion criteria, study participants, setting, HRs, and 95% CIs for CKD, ESRD, IgAN, GD, and death from renal disease. Furthermore, the Newcastle–Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the included cohort studies. The NOS for cohort studies consists of three domains: the selection of research group, comparability, and outcome assessment. Using these criteria, studies were rated a maximum of one star for each question in the selection of the research group and outcome assessment domains. Up to two stars were granted for each question in the comparability domain. Cohort studies with ratings of seven stars or less were viewed as having poor quality.
Review Manager 5.3 (Nordic Cochrane Centre, Cochrane Collaboration, 2014) was used to conduct the meta-analysis. The risk of outcome was presented as a log hazard ratio HR with a 95% CI and standard error for included studies. The I2 statistic was used to assess statistical heterogeneity. Because clinical heterogeneity was expected across included studies, a random-effects model was used for meta-analysis. Furthermore, a stratified analysis was conducted based on psoriasis severity and respective risk estimates for mild psoriasis and severe psoriasis.
| Results|| |
Literature search and characteristics of included studies
[Figure 1] shows the process of literature search and selection of potential studies according to the preferred items for systematic reviews and meta-analysis guidelines. The search identified 831 studies, of which 51 duplicates were removed; 771 others were excluded after screening. After examining the full text of the remaining nine articles, four studies were excluded for failure to meet inclusion criteria. Three of the studies were cross sectional and one addressed cause-specific mortality. Ultimately, five cohort studies were included in the systematic review; however, due to two studies did not have results of subgroup analysis (mild and severe psoriasis), only three of those were included in the final meta-analysis.,,
|Figure 1: Preferred reporting items for systematic reviews and meta-analysis flow chart of study identification.|
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Characteristics of the included cohort studies, which were published from 2013 to 2016, are shown in [Table 1]. Studies were based on population-based databases in the United Kingdom, Taiwan, Sweden, and the United States. Adjustment for age and sex was performed for all three studies. All studies reported HRs for overall psoriasis, mild psoriasis, and severe psoriasis. Furthermore, quality assessment was considered high, as each study had a NOS score of nine stars [Table 2].
Risk of incident chronic kidney disease
The overall HR for CKD in patients with psoriasis was 1.53 (95% CI: 1.20–1.96) with significant heterogeneity [I2 = 95%; P < 0.0001; [Figure 2]]. The random-effects model was used in subgroup analyses to pool HR for severe psoriasis and mild psoriasis [Figure 3]. The pooled HR for severe psoriasis was 1.91 (95% CI: 1.78–2.05), and the I2 value was 0% (P = 0.39). However, there was no difference in the risk of CKD for patients with mild psoriasis compared with patients without psoriasis (pooled HR: 1.14; 95% CI: 0.87–1.48). The I2 value showed that there was high heterogeneity in the HR for mild psoriasis (I2 = 95%; P < 0.0001).
|Figure 2: Meta-analytic estimates of incident chronic kidney disease for patients with psoriasis and controls.|
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|Figure 3: Meta-analytic estimates of incident chronic kidney disease for patients with mild or severe psoriasis and controls.|
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Risk of end-stage renal disease
As shown in [Figure 4], the random-effects model was used to pool the risk for patients with psoriasis compared with patients without psoriasis because of low heterogeneity (I2 = 0%; P = 0.75); the pooled HR was 1.21 (95% CI: 1.03–1.42). A random-effects model was used to analyze the association between ESRD and severe and mild psoriasis [Figure 5]. Meta-analysis showed that the risk of ESRD differed for patients with severe psoriasis compared with those without psoriasis (HR: 2.72, 95% CI: 1.71–4.34) and that there was low heterogeneity in the pooled analysis for risk of ESRD for patients with severe psoriasis (I2 = 21%; P = 0.28). However, the risk of ESRD for patients with mild psoriasis did not differ from that of patients without psoriasis (HR: 1.07; 95% CI: 0.86–1.33), and heterogeneity was 31% (P = 0.24).
|Figure 4: Meta-analytic estimates of end stage renal disease for patients with psoriasis and controls.|
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|Figure 5: Meta-analytic estimates of end stage renal disease for patients with mild or severe psoriasis and controls.|
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Risk of IgA nephropathy and glomerular disease
Grewal et al. demonstrated that psoriasis is a risk factor for IgAN and GD [Table 1]. In that study, the HR for IgAN was 1.37 (95% CI: 0.87–2.18) among all patients with psoriasis but 4.75 (95% CI: 1.92–11.76) among patients with severe psoriasis. For GD, the same study also showed that only patients with severe psoriasis were at increased risk. However, Chiu et al. showed that all patients with psoriasis were at increased risk of GD (HR: 1.50; 95% CI: 1.245–1.81). In subgroup analyses of GD risk, patients with mild psoriasis had a 1.93-fold risk (95% CI: 1.05–3.54), and patients with severe psoriasis had a 1.46-fold risk (95% CI: 1.20–1.78) compared to patients without psoriasis.
Risk of death from kidney disease
Svedbom et al. found that patients with mild psoriasis had 2.20-times the risk of death from kidney disease and that patients with severe psoriasis had 1.87-times the risk of death from kidney disease, compared to patients without psoriasis [Table 1].
Quality of included studies
In [Table 1], we utilized the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence to evaluate the recommend grading and the levels of evidence.
NOS assessment showed that all included studies were rated nine stars and were of high quality [Table 2].
| Discussion|| |
This meta-analysis showed that patients with psoriasis are at higher risk of incident CKD or ESRD. When patients were stratified into mild or severe psoriasis groups based on systemic treatment or phototherapy use, the risk of CKD and ESRD remained significant for those with severe psoriasis. However, the risk of ESRD was comparable to control in mild psoriasis. Besides, due to a high level of heterogeneity, the risk of CKD among patients with mild psoriasis remained inconclusive. In conducting the systemic review, it was shown that the risk of death from renal causes was increased among patients with mild psoriasis, and the risks of IgAN and GDs were increased among patients with severe psoriasis.
Psoriasis, an immune-mediated inflammatory disease that occurs in genetically susceptible persons, is characterized by inflammatory skin plaques. This inflammatory response is initiated and perpetuated by the infiltration of dendritic cells, T-cells, keratinocytes, and neutrophils and the secretion of cytokines from immune cells. Increasing evidence supports an association between psoriasis and multiple comorbidities including CKD and glomerular disorders. The pathogenesis of psoriasis-related renal disease may be related to an increased immunoactivity burden. Hyperuricemia is commonly seen in patients with psoriasis, and treatment toxicity is well-known risk factors for renal disease.,,, In addition, upper respiratory tract infection from Group A beta-hemolytic streptococci may trigger both guttate psoriasis and IgAN in susceptible hosts.
Several studies support an association between CKD and psoriasis, with some showing conflicting results among patients with mild disease. In Taiwan, one nationwide retrospective cohort study indicated that psoriasis was an independent risk factor of chronic renal failure and ESRD. Cyclosporin, a commonly used antipsoriatic agent, did not increase the risk of renal disease in patients with psoriasis significantly. In this meta-analysis, we identified three cohort studies that reported HRs for CKD risk among patients with psoriasis of varying severity.,, Patients with severe psoriasis, defined as a disease requiring the use of systemic treatment or phototherapy, had a higher risk of incident CKD. Although there was no associated risk among patients with mild psoriasis, there was a high level of heterogeneity (I2 = 95%). The included study that used data from the Longitudinal National Health Insurance Research Database in Taiwan showed that CKD was associated with mild psoriasis. Interestingly, another research team that used the same database reached a different conclusion in answering this question. Differences in the use of diagnostic codes for incident CKD and length of the observational period may explain the inconsistency in results. The risk of incident CKD in patients with mild psoriasis may require further clarification.
According to the meta-analysis, the risk of ESRD is increased for patients with severe, but not mild, psoriasis. The levels of heterogeneity are low and intermediate in the two groups (I2 = 21% and 31%, respectively). Interestingly, the risk of death from renal disease was increased in patients with mild, but not severe, psoriasis in a Swedish cohort study. From that registry data, researchers found that patients with psoriasis had a higher risk of death compared to sex-, age-, and residency-matched referents. The main driver of excess mortality was cardiovascular disease, which may be related to an increased prevalence of cardiovascular comorbidities among patients with psoriasis. The risk of death from renal causes was relatively small, only constitutes 1.3% and 1% cause of death, which may compromise the statistical power. Besides, renal death was largely determined by patients' willingness and the periprocedural complications of renal replacement therapy, rather than the disease severity itself. Thus, the association between renal disease as a cause of death and psoriasis needs further evaluation.
Two cohort studies have shown an increased risk of GD among patients with psoriasis., However, those with mild psoriasis were not at increased risk. In the Taiwan cohort, Chiu et al. showed an increased risk (HR = 1.93; 95% CI: 1.05–3.54) of GD in patients with mild psoriasis. In contrast, Grewal et al. did not find this association in the United Kingdom cohort. Although both study teams identified GD using diagnostic codes and defined severe psoriasis by the use of systemic treatment or phototherapy, the GD occurred in only 0.05% of patients in the United Kingdom but 2.8% of patients in Taiwan. Although not discussed in the Taiwan cohort study, IgAN has been shown to be more prevalent among East Asians. Therefore, a higher genetic susceptibility may account for the increased risk of GD in the Taiwan cohort., For the two studies we identified during the systemic review, it is still insufficient to conclude the causal association between GDs and the severity of psoriasis. More studies are needed to clarify this question.
This study has several limitations. First, the retrospective nature of the included cohort studies prevents the establishment of a causal relationship between psoriasis and renal disease. Second, all studies defined patients and outcomes using diagnostic codes, without the use of relevant clinical variables such as laboratory data and pathologic findings. Thus, misclassification bias may have occurred. Third, most studies used treatment patterns, instead of the percentage of skin involvement, to classify severity. Fourth, although most studies compared patients with psoriasis with age- and sex-matched controls and adjusted for known risk factors, bias resulting from unknown confounders could not be excluded. Fifth, we are not able to evaluate the time course of the onset of renal diseases after the diagnosis of psoriasis due to the nature of this study. Further studies are needed to evaluate this clinically important question. Sixth, I2 test seeks to determine whether there are real differences according to the results of the selected studies, namely, heterogeneity, or whether the variation in findings is reconcilable with chance alone, that is, homogeneity. I2 values of 0%–24.9%, 25%–49.9%, 50%–74.9%, and 75%–100% were viewed as none, low, moderate, and high heterogeneity, respectively. In this study, we used the random-effects model when I2 statistics were 95% more than 75% [Figure 2] and [Figure 3]. However, we aggregate studies that are different methodologies; heterogeneity in the results is still inevitable.
| Conclusion|| |
This study provides evidence that the risks of CKD, ESRD, and GDs are increased in patients with severe psoriasis. As the prevalence of psoriasis rapidly expands and causes a major impact on the quality of life for affected patients, prevention and care for patients with CKD have become public health priorities. In patients with severe psoriasis, regular assessment of renal function, restrictive use of nephrotoxic drugs, and timely referral for renal evaluation should be essential parts of disease management. However, the association between renal disease and mild psoriasis is less consistent. A further study focusing on patients with mild psoriasis using a longer observational period is needed to clarify this question.
Financial support and sponsorship
Conflicts of interest
Prof. Ching-Chi Chi, an associate editor of Dermatologica Sinica, had no role in the peer review process of or decision to publish this article.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]