Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.

BackgroundFabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene, followed by deficiency in α-galactosidase A (α-gal) activity. Nephrotic syndrome, as the renal phenotype of FD, is unusual. Here, we report the rare case of a patient with FD with nephrotic syndrome whose proteinuria disappeared by immunotherapy.Case presentationA 67-year-old Japanese man was admitted to our hospital because of emesis, abdominal pain, and facial edema due to nephrotic syndrome. The patient was diagnosed with focal segmental glomerulosclerosis (FSGS) by renal biopsy before being diagnosed with FD, and immunotherapy was initiated. After treatment, the kidney biopsy results showed typical glycosphingolipid accumulation in the podocytes of this patient. The white blood cell α-gal activity was very low, and genetic analysis revealed a GLA gene variant (M296I), which is known as a late-onset genetic mutation of FD. Immunotherapy (steroids and cyclosporine A) dramatically improved the massive proteinuria. Currently, he has been undergoing enzyme replacement therapy, and his proteinuria has further decreased. There is the possibility that other nephrotic syndromes, such as minimal change nephrotic syndrome or FSGS, may co-exist in this patient.ConclusionsWe experienced the rare case of a FD patient whose nephrotic syndrome disappeared by immunotherapy. These findings suggest that immunosuppressive treatment may be considered if nephrotic syndrome develops, even in patients with FD.

Background Fabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0–1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1–5 is unknown. Methods Serum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1–5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1–5 was evaluated. Results FD prevalence rates in patients with CKD Stage 5D and CKD Stages 1–5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1–5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1–5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001). Conclusions FD prevalence was much higher in male patients with CKD Stages 1–5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1–5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.

We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING) with overexpression of glomerular advanced glycation end products (AGEs) and their receptor (RAGE). A 59-year-old Japanese man with nephrotic syndrome, who had a smoking history of one pack of cigarettes per day for approximately 40 years, presented with a 3-year history of urinalysis abnormalities without clinical evidence of diabetic mellitus. The patient's leg edema progressively worsened over the previous 2 years, and he was admitted to our hospital. Renal biopsy showed mesangial expansion with diabetic Kimmelstiel-Wilson-like nodular lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron microscopy. Skin AGE level measured using AGE reader was higher in this case than the average level in age-matched Caucasians. In addition, immunohistochemical analysis revealed that N-carboxymethyl lysine, one of the major AGEs, and RAGE were overexpressed and podocin expression was decreased in the peripheral area of the glomerular nodular lesions. These observations suggest that AGEs-RAGE system may be activated in smoking-related ING, possibly leading to the progression of renal dysfunction.

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Background and aim: Carnitine deficiency is common and associated with muscle atrophy in hemodialysis (HD) patients. We investigated whether carnitine levels could be an independent predictor for exercise capacity in these patients. Method: A total of 37 patients (mean age, 55.9 ± 13.4 years) who underwent HD three times a week were enrolled in this study. Carnitine fraction levels were measured by the enzyme cycling method. Univariate and multiple stepwise regression analyses were performed to determine the correlation between free carnitine levels and the value of exercise capacity examined by the time-up-and-go test (TUG), knee extension strength, functional reach test (FRT), and 10-m walk test, and thigh and calf circumferences as markers of muscle mass. Results: Serum free carnitine levels were significantly decreased in HD patients. Free carnitine levels were associated with TUG (inversely; r 2 = 0.120, P = 0.035), knee extension strength (r 2 = 0.129, P = 0.029), FRT (r 2 = 0.246, P = 0.002), and the 10-m walk test (inversely; r 2 = 0.149, P = 0.018). Multiple stepwise regression analysis revealed that free carnitine was an independent predictor for FRT (β = 0.369, P < 0.001). There was no correlation between free carnitine levels and thigh and calf circumferences. Conclusion: Low serum free carnitine levels were associated with decreased exercise capacity in HD patients, suggesting that carnitine deficiency may be a promising therapeutic target for HD-associated muscle weakness in HD patients. This study was retrospectively registered.

Background Etelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety and efficacy of replacing cinacalcet with etelcalcetide in HD patients. Methods One hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively. Results Of the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (p < 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients, p = 0.087; 90 patients, p < 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed. Conclusions This study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet. Trial registration UMIN, UMIN000027637; Registered on June 5, 2017.

Table 3. Summary of the recent screening for FD in male patients with CKD Stage 5D No. Authors Country Date of publication No. of total male patients Screening method of a-Gal A activity Gene mutations (No. of patients) Prevalence of FD without functional variants (%) Red: Classic Blue: Late-onset Green: Unknown Black: Functional variants 1 Utsumi K et al. [20] Japan 2000 440 Plasma p. Gln357Xaa (1) N/A (1) 2/440 (0.45) 2 Nakao S et al. [21] Japan 2003 514 Plasma p.Gly373Asp (1) p.Met296Ile (3) p.Ala97Val (1) p.Glu66Gln (1) 5/514 (0.97) 3 Linthorst GE et al. [22] Netherlands 2003 508 Whole blood p.D299E (1) 1/508 (0.20) 4 Kotanko P et al. [23] Austria 2004 1,516 DBS test p.Ala121Pro (1) p.Trp162Arg (1) p.Ile239Thr (1) p.Arg112His (1) 4/1,516 (0.26) 5 Ichinose M et al. [24] Japan 2005 450 Plasma c.761_763delTTG (1) 1/450 (0.22) 6 Tanaka M et al. [25] Japan 2005 401 Plasma p.Tyr365Xaa (2) 288AAT-AT(DelA) (1) a p.Met296Ile (1) 4/401 (1.00) 7 Bekri S et al. [5] France 2005 59 Blood leukocytes p.Asn215Ser (1) 1/59 (1.69) 8 Merta M et al. [26] Czech Republic 2007 1,521 DBS test p.Gly360Ser (1) p.Ile317Thr (1) p.Arg112His (1) p.Ala143Thr (1) 3/1,521 (0.20) 9 Porsch DB et al. [27] Brazil 2008 558 DBS test N/A (1) N/A (1) 2/558 (0.36) 10 Terryn W et al. [28] Belgium 2008 180 DBS test p.Trp236Arg (1) 1/180 (0.56) 11 Andrade J et al. [4] Canada 2008 499 Plasma N/A (0) 0/499 (0) 12 Fujii H et al. [29] Japan 2009 635 DBS test p.Glu66Gln (1) 0/635 (0) 13 Gaspar P et al. [30] Spain 2010 543 DBS test c.1037delG (1) p.Asp313Thr (1) p.Arg118Cys (2)