Kidney
The kidneys filter blood, regulate fluid and electrolyte balance (sodium, potassium, calcium, phosphate), and activate vitamin D. They also produce erythropoietin, stimulating red blood cell production, and renin, which triggers the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure and sodium retention.
Metabolic connections
[edit]Kidney function is tied to thyroid status: hypothyroidism reduces renal blood flow and glomerular filtration rate, and can elevate creatinine independent of muscle mass changes. High cortisol and aldosterone, both increased under chronic stress, increase sodium retention and potassium loss through the kidney.
Chronic kidney disease
[edit]A 24-week RCT in moderate chronic kidney disease found lubiprostone (8 or 16 mcg daily) slowed estimated glomerular filtration rate decline versus placebo, with the higher dose most effective consistent with constipation relief lowering gut-derived inflammatory burden on the kidney.[1] Compromised intestinal barrier function in type 2 diabetes correlated with higher LPS and TLR4 activation and independently predicted microalbuminuria.[2] Glycine supplementation reversed advanced diabetic kidney lesions in db/db mice, paralleling canagliflozin-induced fasting-like renal metabolic shifts away from fatty-acid oxidation.[3] Combined dihydrotestosterone and anastrozole in streptozotocin-diabetic male rats restored renal AR/ERα balance and abolished progression of albuminuria, inflammation, and tubulointerstitial fibrosis beyond either treatment alone.[4] Mineralocorticoid receptor (MR) overactivation from aldosterone and, in its absence, from cortisol contributes to chronic kidney disease progression in type 2 diabetes. The MR antagonist finerenone reduced kidney and cardiovascular events in the FIDELIO-DKD trial of patients with type 2 diabetes and CKD.[5]
NAD+ and tubular mitochondria
[edit]Human diabetic and hypertensive kidney disease shows reduced NAD+ with impaired mitochondrial gene expression in tubular cells NAD+ precursor supplementation (nicotinamide riboside or NMN) protected tubular mitochondria and prevented kidney disease in mice.[6]
Testosterone and CKD risk
[edit]Observational evidence links low serum testosterone to higher incident CKD in the general population (HR 1.38 vs normal range) and to roughly doubled all-cause mortality and cardiovascular-event risk in men with established CKD DHEAS showed mixed associations.[7]
Gut motility and mitochondrial function
[edit]In a randomized phase 2 trial of 150 patients with stage IIIb-IV chronic kidney disease, the constipation drug lubiprostone (16 mcg) slowed decline in estimated glomerular filtration rate versus placebo over 24 weeks. The mechanism traced to the gut microbial agmatine pathway raising spermidine, which improved renal mitochondrial function -- consistent with reduced endotoxin/LPS absorption from improved gut motility as a systemic driver of kidney damage.[8]
Kidney stones
[edit]Kidney stones are mineral crystals in the urinary tract, commonly calcium oxalate; hydration, oxalate load, citrate, and calcium intake pattern matter. The same diet that protects against osteoporosis (plenty of protein and calcium) also protects against kidney stones and other abnormal calcifications.[9] Medical care is needed for acute stones; balance calcium food intake with oxalate load.
See also
[edit]References
[edit]- ↑ Watanabe T, et al. "Lubiprostone in chronic kidney disease," Sci Adv. 2025. doi:10.1126/sciadv.adw3934.
- ↑ Zhang L, et al. "LPS-TLR4 signaling and microalbuminuria in T2DM," Diabetes Metab Syndr Obes. 2022. doi:10.2147/DMSO.S377776.
- ↑ Shao Y, et al. "Glycine in diabetic kidney disease," Diabetologia. 2024. doi:10.1007/s00125-023-06078-0.
- ↑ Garjani A, et al. "DHT plus anastrozole reverses diabetic nephropathy in male rats," Am J Physiol Renal Physiol. 2012;302(2):F271-F280. doi:10.1152/ajprenal.00569.2011.
- ↑ Bakris GL, et al. "Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes," N Engl J Med. 2020;383(23):2219-2229.
- ↑ Zhao Y, et al. "NAD+ deficiency in kidney disease," Nat Commun. 2023. PMID 36914910.
- ↑ Carrero JJ, et al. "Testosterone and kidney disease: a systematic review and meta-analysis," J Clin Endocrinol Metab. 2022. PMID 35551117.
- ↑ "Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial," Sci Adv. 2025.
- ↑ Ray Peat, "Bone Density, Bone Loss: First, Do No Harm." "The same diet that protects against osteoporosis, i.e., plenty of protein and calcium, etc., also protects against kidney stones and other abnormal calcifications."