Nephrosclerosis shows an increasing trend as a disease, leading to the initiation of dialysis. The main cause of nephrosclerosis is hypertension, but factors that promote arteriosclerosis, such as aging, are also involved. In addition, hyperuricemia-associated renal injury is known to show renal pathological features of nephrosclerosis. We examined renal biopsy specimens from two patients who presented with hyperuricemia and rapid renal decline without hypertension or glomerulonephritis. Case 1 was a 59-year-old man. Hypertension was well-controlled with medication. Case 2 was a 41-year-old woman. She was previously diagnosed with renal injury and hyperuricemia during pregnancy. Case 1 showed a decrease in eGFR of 17 mL/min/1.73 m² over 2 years, and case 2 showed a decrease in eGFR of 5 mL/min/1.73 m² over 1 year, indicating a progressive decline in the renal function. In these cases, blood pressure was normal or well-controlled, with scanty urine findings. Renal pathological findings showed glomerulosclerosis and glomerulomegaly. Interstitial fibrosis and tubular atrophy were noted around the glomerulosclerosis. No vascular lesions were seen. Glomerulomegaly suggested the presence of glomerular hyperfiltration, and hyperuricemia was suspected as a cause of nephrosclerosis. The family history of renal disease was unclear, and the involvement of autosomal dominant tubulointerstitial kidney disease could not be ruled out. Renal injury associated with hyperuricemia is characterized by vascular lesions, nephrosclerotic lesions, and tubulointerstitial injury, but the pathogenesis remains unclear. The management of asymptomatic hyperuricemia with renal injury requires further study.

Hyperuricemia is a strong risk factor for renal dysfunction, but the effect of uric acid-lowering agents on the renal function has not been uniformly demonstrated. The aim of this study was to evaluate the effect of the novel uricosuric agent dotinurad on serum uric acid (SUA) levels and the estimated glomerular filtration rate (eGFR) in patients with hyperuricemia. A cohort of 40 patients with reduced renal excretion of uric acid were enrolled, including 19 patients with chronic kidney disease (CKD). Patients started taking dotinurad at 0.5 mg/day and the dose was adjusted to achieve SUA levels of 6.0 mg/dL or lower.

Twenty-four weeks after starting the administration of dotinurad, its mean daily dose was 1.15±0.57 mg and the rates of achieving SUA at 6.0 mg/dL or lower were 50% in the 0.5-mg group, 78.9% in the 1-mg group, and 90.9% in the 2-mg group. The SUA level significantly decreased from 8.28±0.70 to 5.50±0.85 mg/dL (p<0.01) and eGFR significantly increased from 62.3 ±15.4 to 65.8±15.7 mL/min/1.73 m² (p<0.01). A significant reduction in the SUA level (8.42±0.71 to 5.86±1.02 mg/dL, p<0.01) and significant increase in eGFR (47.4±10.4 to 53.2±13.3 mL/min/1.73 m², p<0.01) were also observed in patients with CKD. The degree of increase in eGFR after starting the administration of dotinurad was correlated with the degree of decrease in serum UA (p<0.05) and eGFR at the baseline (p=0.02) in patients with CKD. Dotinurad administration to patients with hyperuricemia, including CKD patients, resulted in favorable SUA levels and improvement in the renal function.

In recent years, it has been reported that fluctuation ranges of various metabolic factors are associated with prognosis. In the present study, we examined serial changes in the fluctuation ranges of serum uric acid levels and uric acid excretion in patients with (n=8) and without (n=6) oral SGLT2 inhibitors. The results showed that the median serum uric acid level was significantly lower in the SGLT2 inhibitor group (5.7+/-0.6 vs. 4.4+/-0.7, p<0.01), and the variability was significantly reduced (1.5+/-0.3 vs. 1.0+/-0.3, p<0.05). This was attributed to significantly lower maximal uric acid levels in the SGLT2 inhibitor group (6.5+/-0.7 vs. 4.9+/-0.8, p<0.01). The median FEUA was higher in the SGLT2 inhibitor group (6.8+/-2.2 vs. 10.3+/-2.7, p<0.03), but the median urinary UA/Cr ratio was similar between the two groups (0.49+/-0.11 vs 0.56+/-0.12, p=0.282). The fluctuation range of the urinary UA/Cr ratio was significantly reduced in the SGLT2 inhibitor group (0.40+/-0.09 vs 0.23+/-0.04, p<0.03), and the minimum urinary UA/Cr ratio was significantly increased (0.31+/-0.09 vs 0.43+/-0.10, p<0.03), which was contributed to the reduced of fluctuation range. Although SGLT2 inhibitors have been reported to suppress the frequency of gout attacks and reduce nocturnal hypertension, further epidemiological studies are needed to determine whether the observed reduction in the fluctuation range of serum uric acid levels is related to the suppression of cardiovascular events or merely on incidental phenomenon.

Purines in foods are present as nucleic acids and umami components such as inosine monophosphate (IMP), guanosine monophosphate (GMP), and xanthosine monophosphate (XMP), and it has been reported that different types of purines have varying effects on serum uric acid levels. This study aimed to clarify the total purine content, as well as molecular-specific contents of nucleotides, nucleosides, and nucleobases, in instant cup noodles, ramen soup from specialty and convenience stores, and seasoning soups for hot pots, to aid dietary guidance for patients with hyperuricemia and gout. According to the classification reported in the guidelines' appendix, the total purine content in these per 100 g ranged from very low to moderate (up to 200 mg/100 g). Ramen soups in specialty stores have a higher total purine content per serving than others due to larger broth volumes (some exceeding 300 g) and rich broths made from animal sources like pork bones, chicken carcasses, and seafood, rather than seasoning extracts. In terms of molecular types, instant cup noodles, convenience store ramen soup, and seasoning soups for hot pots contained more umami components such as IMP and GMP. On the other hand, ramen soups from specialty stores varied in their molecular contents depending on the store, with some soups containing more inosine and hypoxanthine than nucleotides. Since hypoxanthine particularly raises serum uric acid levels in gout patients, it is recommended that patients with hyperuricemia and gout limit their frequency of consuming ramen from specialty stores and reduce the amount of soup consumed per serving.

While hyperuricemia is known to indicate a poor prognosis in hospitalized patients, factors determining its onset during hospitalization remain unclear. In this study, we used a machine learning-based statistical model to identify and combine factors predicting hyperuricemia. We enrolled 595 patients hospitalized at NHO Yonago Medical Center. Hyperuricemia (serum uric acid level >7.0 mg/dL) was the dependent variable, while age, sex, emaciation, medical history, medication, and biochemical data were independent variables. We used the machine learning-based statistical model to classify predictive factors and combined them using a decision tree based on the XGBoost model. Compared with normouricemic patients, hyperuricemic patients had significantly higher BMI and higher incidences of obesity, hypertension, diabetes, and treatment with ST-combo, diuretics, beta-blockers, and ACE inhibitors. They also had significantly lower serum K levels and eGFR. The XGBoost model showed a higher AUC value compared with logistic analysis in predicting hyperuricemia. SHAP values indicated that the main predictive factors were: creatinine, diuretics, eGFR, BUN, serum K level, age, AST, and ALT. The decision tree revealed that in patients not on diuretics, hyperuricemia could be predicted by either a combination of higher serum K levels and younger age or lower serum K levels and higher BUN levels. In patients on diuretics, a combination of higher creatinine levels and lower ALT levels was predictive of hyperuricemia. In conclusion, the XGBoost model effectively identified and combined factors to predict hyperuricemia in hospitalized patients.