UNIVERSITY Health Kidney Interpretation and Intervention Lesson Overview Functions of the Kidney How the Kidney Works AAS and GH Impact on Kidney Dose Type and Dosage of AAS Matter? Signs of Kidney Dysfunction- Lab work Kidney Lab interpretation Kidney Health Intervention Strategies Functions of the Kidney Prime function is balance of fluids, electrolytes, and organic solutes via continuous filtration of blood Filters 180L of blood per day into ultrafiltrate which is further turned into the 1.5L of urine excreted per day Waste removal of uric acid, ammonia, and creatinine Maintains body pH via excretion of H+ ions and reabsorption of bicarbonate Regulation of Blood Pressure via secretion of Renin > Angiotensin (vasoconstriction) > Aldosterone (sodium and water reabsorption) Secretes Erythropoietin and Calcitriol (1,25[OH]2 Vitamin D3 (Ca/P homeostasis) Regulation of blood volume via Vasopressin from the hypothalamus causing increased water reabsorption How the Kidney Works Kidney composed of 1million nephrons, one part damaged, nephron is nonfunctional Glomerulus produces the ultrafiltrate contains Podocytes with AR and ER Tubules is site of electrolyte exchange and urine formation A Primer into Lab Work AAS and GH Impact on Renal Function Case Studies Hertlitz et al 2010 focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient Among eight patients with mean followup of 2.2 yr, one progressed to ESRD ARB main treatment modality Average BMI 34.7kg/m2 AAS and GH Impact on Renal Function Case Studies El-Reshaid et al 2018, Prospective Study of 22 male Bbers Dosages of testosterone 250mg/day on average 100mg/day Greater exposure time presented with greater renal damage Hypertensive changes were present in all patients How PEDs Effect the Kidney Acute Kidney Injury (AKI): acute decrease in Glomerular filtration rate (GFR) GFR: amount of filtrate per unit in the nephrons, typically estimated from serum creatinine Causes can be classified into categories: Prerenal: dehydration, hypercalcemia, vitamin D toxicity, liver cholestasis (17aa oral AAS) Intrinsic: Acute tubular Necrosis, interstitial nephritis, Rhabdomyolysis Post renal:, BPH Urinary tract obstruction How PEDs Effect the Kidney Chronic Kidney Disease (CKD) Gradual loss of kidney function Diabetes and Hypertension leading cause Renal Blood Pressure regulation: AAS upregulation of RAAS increase BP and sodium retention Increased Endothelin = increased vasoconstriction Oxidative Stress: increased ROS Apoptosis and Inflammatory cytokines: Increased TNF alpha and IL6, cell death of podocytes and glomerulosclerosis (renal scarring) Kidney contains GH, IGF1 receptors along with AR, ER receptors, GH can activate RAAS increasing BP Estrogen is kidney protective Increase in lean body mass and high protein intake can result in glomerular hyperfiltration TRT therapy renal protective PED Dose Effect Animal model: “Effect of Nandrolone Decanoate, Boldenone Undecylenate on Renal Status of Rabbits” Nandrolone Decanoate (ND) 4.5mg/kg body wt Boldenone Undecylenate (BOL) 10mg/kg body wt and combination of both (ND+BOL) 14.5 mg/kg body wt on renal system of male rabbits Nandrolone and boldenone alone lead to similar creatinine levels, while the combination lead to the greatest increase in creatinine Human model: “Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders” Group (n=8, intramuscular 500mg testosterone enanthate, intramuscular 400 mg nandrolone decanoate and oral 40 mg methandrostenolone for 12 weeks), Group (n=7, intramuscular 500 mg testosterone enanthate, intramuscular 300 mg nandrolone decanoate and intramuscular 300 mg boldenone undecylenate for 16 weeks) Group (n=7, no steroid intake) Plasma levels of BUN and creatinine were increased in group (P ˂ 0.001) compared the other groups (Table 1) Right and left kidney grade, the thickness of renal parenchyma and renal volume were significantly increased in group Lab Tests and Abnormalities Kidney Function Test: Lab test Range interpretation Creatinine 0.8-1.5mg/dL Byproduct of creatine, higher with increased lean body mass Represent renal filtration BUN 6-20mg/dL Reflection of liver and kidney function, high in dehydration and high protein intakes (HYDRATE PRIOR TO LAB TESTING) BUN/Creatinine 6-28 ratio Determine cause of renal issue >20 prerenal dehydration 60-90ml/min/1.732 Calculated by creatinine, age and gender Albumin serum 3.5-5.2g/dL Low in kidney disease, increased protein loss in urine Calcium, serum 8.5-10.5mg/dL High in vitamin D toxicity, nephrocalcification Phosphorus, serum 2.5-4.5mg/dl Increased in kidney disease Sodium, serum 133-146meq/L Fluid balance kidney regulated Hypo or hyperhydration, tightly regulated Potassium, serum 3.5-5.4meq/L Inversely related to sodium, increases cause aldosterone release, high in kidney failure 25 OH D 40-60ng/ml High or low dependent on vitamin D intake Glomerular Filtration Rate We rely heavily on this measure for prediction of renal function Normal 90-120ml/min/1.732 GFR in lab work is estimated (eGFR) over directly measured eGFR is based on serum, creatinine levels In athletes eGFR may be underestimated using creatinine due to increased muscle mass and creatine supplementation Cystatin-C based eGFR formula may be a more accurate measure of kidney function Serum creatinine, can also remain wnl, and not represent true decrease in renal functional decline Kidney Health Intervention Dyslipidemia, Hypertension and Diabetes are independent risk factors for CKD, follow all previous recommendations around the topics a few repeats will occur Blood pressure and blood sugar control essential Dietary Interventions HYDRATION Protein intake 1-1.5g/lb is acceptable and safe Increase fruit and vegetable intake Limit excessive salt intake if responsive Increase nitrate rich foods (beets, spinach, arugula) Supplement Strategies *review hypertension supps (omega 3, vitamin D +K2, cocoa, garlic, CoQ10, beet root) Monitor excessive Vitamin D and calcium intakes Curcumin 1500mg (intestinal barrier strengthening, decreased TNF alpha and IL-6, decrease ROS) Grape Seed Extract 1-2g/day (anti-inflammatory and anti-oxidant) Arjuna 500mg (reduce oxidation) Astragulus Membranaceus 4-6g/day (increase ANP, decrease cytokines) Kidney Health Intervention PED Interventions Limit 17aa orals as they increase risk of AKI cholestasis Renal toxicity is dose responsive, limit doses and duration of use Estrogen is renal protective, don’t over suppress Estradiol Potential for Boldenone to be more renal toxic, (not human use approved) Drug Intervention Blood pressure medications Telmisartan BP med of choice (Angiotensin II receptor blocker) Metabolic effects: Increase Peroxisome Proliferator activated receptor gamma and delta (PPAR)= increased insulin sensitivity, reduces dyslipidemia, increased HDL, decreased visceral fat, increased fatty acid oxidation Vascular effects: prevention of vascular smooth muscle cell proliferation greater than other ARBs Renal effects: Lowers BP via Renin angiotensin aldosterone system (RAAS), prevents fibrosis, decrease TGF-beta, decreased oxidative stress References Faria, João & Ahmed, Sabbir & Gerritsen, Karin & Mihaila, Silvia & Masereeuw, Rosalinde (2019) Kidney-based in vitro models for drug-induced toxicity testing Archives of Toxicology 93 10.1007/s00204-019-02598-0 Mahan, KL Krause’s Food and Nutrition Care Process 13th edition Elsevier: USA, 2012 Herlitz LC, Markowitz GS, Farris AB, et al Development of focal segmental glomerulosclerosis after anabolic steroid abuse J Am Soc Nephrol 2010;21(1):163-172 doi:10.1681/ASN.2009040450 El-Reshaid W, El-Reshaid K, Al-Bader S, Ramadan A, Madda JP Complementary bodybuilding: A potential risk for permanent kidney disease Saudi J Kidney Dis Transpl 2018 MarApr;29(2):326-331 doi: 10.4103/1319-2442.229269 PMID: 29657200 Davani-Davari D, Karimzadeh I, Khalili H The potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the kidney: a systematic review BMC Nephrol 2019 May 31;20(1):198 doi: 10.1186/s12882-019-1384-0 PMID: 31151420; PMCID: PMC6545019 Shabir N et al Effect of Nandrolone Decanoate, Boldenone Undecylenate on Renal Status of Rabbits (Oryctolagus cuniculus Global Veterinaria 14 (3): 432-438, 2015 DOI: 10.5829/idosi.gv.2015.14.03.92201 Kantarci UH, Punduk Z, Senarslan O, Dirik A Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders J Sports Med Phys Fitness 2018 Nov;58(11):16811687 doi: 10.23736/S0022-4707.17.06763-9 Epub 2017 Nov 17 PMID: 29148625 References Banfi G, Del Fabbro M, Lippi G Relation between serum creatinine and body mass index in elite athletes of different sport disciplines Br J Sports Med 2006 Aug;40(8):675-8; discussion 678 doi: 10.1136/bjsm.2006.026658 Epub 2006 May 24 PMID: 16723402; PMCID: PMC2579448 Beetham KS, Howden EJ, Isbel NM, Coombes JS Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease BMC Nephrol 2018;19(1):366 Published 2018 Dec 18 doi:10.1186/s12882-018-1146-4 Ghosh SS, Gehr TW, Ghosh S Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase Molecules 2014;19(12):2013920156 Published 2014 Dec doi:10.3390/molecules191220139 Turki K, Charradi K, Boukhalfa H, Belhaj M, Limam F, Aouani E Grape seed powder improves renal failure of chronic kidney disease patients EXCLI J 2016 Jun 27;15:424-433 doi: 10.17179/excli2016363 PMID: 27822171; PMCID: PMC5083963 Li M, Wang W, Xue J, Gu Y, Lin S Meta-analysis of the clinical value of Astragalus membranaceus in diabetic nephropathy J Ethnopharmacol 2011 Jan 27;133(2):412-9 doi: 10.1016/j.jep.2010.10.012 Epub 2010 Oct 13 PMID: 20951192 Ladino M, Hernandez Schulman I Renovascular and renoprotective properties of telmisartan: clinical utility Int J Nephrol Renovasc Dis 2010;3:33-38 doi:10.2147/ijnrd.s7033 Chujo D, Yagi K, Asano A, Muramoto H, Sakai S, Ohnishi A, Shintaku-Kubota M, Mabuchi H, Yamagishi M, Kobayashi J Telmisartan treatment decreases visceral fat accumulation and improves serum levels of adiponectin and vascular inflammation markers in Japanese hypertensive patients Hypertens Res 2007 Dec;30(12):1205-10 doi: 10.1291/hypres.30.1205 PMID: 18344626  ... Functions of the Kidney How the Kidney Works AAS and GH Impact on Kidney Dose Type and Dosage of AAS Matter? Signs of Kidney Dysfunction- Lab work Kidney Lab interpretation Kidney Health Intervention... Effect the Kidney Chronic Kidney Disease (CKD) Gradual loss of kidney function Diabetes and Hypertension leading cause Renal Blood Pressure regulation: AAS upregulation of RAAS increase BP and sodium... intramuscular 400 mg nandrolone decanoate and oral 40 mg methandrostenolone for 12 weeks), Group (n=7, intramuscular 500 mg testosterone enanthate, intramuscular 300 mg nandrolone decanoate and intramuscular