Among these Iraqi Kurdistan bodybuilders, renal disease rates, except for nephrocalcinosis, were similar to those found in the age-matched, general male population. Nephrocalcinosis was a uniquely bodybuilding disease and was found only with injections of veterinary grade vitamin D compounds. It did not occur in everyone using veterinary compounds but had an estimated 9-year cumulative occurrence of one per 314 vitamin D injectors. Of the two nephrocalcinosis patients in this study, one required transplantation, and the other, one year after diagnosis, had moderately advanced, although apparently stable, chronic kidney failure. The absence of clinical disease in the majority of vitamin D injectors and the stability of disease in one of our patients suggests that nephrocalcinosis might be manageable or even avoidable with early intervention. For the level of anabolic steroid use practiced in the region, that includes multiple drugs simultaneously in 10% of bodybuilders, the frequency of FSGS among bodybuilders could not be considered any greater than the general population risk.
ATN was the most common type of renal disease encountered among our bodybuilders and occurred at an annual rate of one per 71,000 gymnasium participants. Acute kidney injury (AKI) in the developing world is a major current interest in nephrology, particularly among the young, because it identifies a group that may have preventable disease .
We commonly see elevated creatinine levels in laborors and soldiers during the summer months, but AKI in these as well as trauma patients is treated on the basis of clinical findings and laboratory chemistries, and patients are not biopsied. Patients with evidence of AKI are biopsied if there is no apparent underlying cause, and these biopsied patients represent our estimates of the incidence of ATN in our general 15–39 year old male population. Among the bodybuilders with ATN, the elevations in creatinine were substantial, averaging 4.1 mg/dL and ranging from 2.6 to 8.6 mg/dL, values well above the lower criteria for AKI in KDIGO Clinical Practice Guidelines .
Data on the rates of AKI for young males is not readily available, but the 1996 study by Liano et al.  may provide a rough estimate of this frequency. These authors report an annual clinical incidence for ATN of 8.8 patients per 100,000 persons who were admitted at an average of 63 ± 17 years of age to hospitals in the Madrid region of Spain. If the proportion of AKI patients under 44 years old is 21% and the proportion with no associated disease is 50% as reported by Shawney et al. , the incidence of ATN for 34 young patients with no comorbid disease would be approximately 0.9 (0.6 to 1.2) patients per 100,000 Madrid residents . This is higher that than the biopsy incidence of ATN at 0.3 (0.1 to 0.5) per 100,000 among the general Kurdish male population but also indicates that biopsy determinations of ATN underestimate its clinical incidence.
Two of the ATN patients we report recently began bodybuildng and presented with muscle pain and evidence of rhabdomyolysis. Muscle pain commonly occurs with new weight lifting regimens and is attributed to microscopic muscle damage [17,18]. This is referred to as exertional muscle injury and is usually accompanied by elevations in serum creatine kinase . Less commonly myoglobin is elevated, with the latter marker being of particular concern because of its association with kidney injury . In the new bodybuilders, ATN may have been the result of excessive muscle damage resulting from overexertion for the person’s level of training.
Muscle pain was not acknowledged by patients with ATN who were regular bodybuilding participants. The cause of this kidney injury is obscure, and it is uncertain whether their ATN is related to bodybuilding or part of an unidentified AKI occurring in the general community. The biopsies of ATN among these more experienced bodybuilders contained microcalcifications, and all patients consumed commercial vitamin and mineral capsules as well as protein and creatine powders. Nevertheless, all of this consumption was well within amounts that, individually or together, are not known to adversely affect kidney function [19,20,21]. It is likely that microcalcifications were the result of dystrophic calcification of cells damaged by a previously unknown insult and not an indication of a primary role of calcium in the kidney injury 
While patients with ATN in our current study presented as acute renal insufficiency, most had histologic evidence of chronic injury suggesting prior kidney damage. Patients with community acquired AKI have up to three times the rate of ESRD as the general population, with the ESRD being primarily related to advanced age and high rates of cardiovascular disease. [22,23]. Whether the risk applies to younger patients is not clear, but baseline normal renal function associates with a decreased risk of ESRD over time [23,24]. This implies that the prognosis in otherwise healthy young men will not be compromised if the injury is not repeated.
In some cases, the pathology underlying the AKI in bodybuilders has been a TIN resembling a drug-type allergy in which the renal failure resolves when supplements are discontinued [25,26]. This TIN is uncommon and, in the current study, occurred at an annual rate of 1 per 200,000 gymnasium users, a frequency not different than TIN in the general population.
FSGS has been linked to anabolic steroid use, and there is experimental evidence that anabolic steroids may be toxic to podocytes [6,7,8]. While this suggests a mechanism of injury, the primary association between anabolic steroids and FSGS, comes from case studies and particularly the 2011 report by Herlitz et al.  of six white and four Hispanic bodybuilders or power lifters aged 28 to 45 years old that developed FSGS after years of training that included using multiple anabolic steroids. This cohort consisted of nine patients from New York City (NYC) and one from Boston that was collected over a 10 year period at three major reference centers and presumably reflects the collective experience of nephrologists and pathologists in the region.
The use of anabolic steroids among males in NYC is probably similar to the 2–4% that is estimated for the US as a whole [27,28]. In this case, the population of anabolic steroid users in the 2011 NYC population of 1.65 million males 20–49 years old would be approximately 31,400 . The nine NYC patients in the paper by Herlitz et al. (7) would then calculate to an annual ASIR of 2.9 (1.0 to 4.8) patients per 100,000 steroid users.
The diagnosis of FSGS has been increasing over the last 20–30 years, and FSGS is now the major cause of nephrotic syndrome in the US and in several other parts of the world, including Iraq [9,30,31]. The incidence of FSGS has been estimated from biopsy series from the Mayo Clinic for Olmstead County, Minnesota and from Melbourne, Australia [32,33].
The FSGS estimate of 2.9 (1.0 to 4.8) per 100,000 NYC body builders may indicate an increased risk when compared to the all age and both gender FSGS incidence of 1.1 (0.7 to 1.5) per 100,000 persons in Olmstead County . It does not indicate a significantly increased risk when compared to the FSGS rate of 1.9 (1.3 to 2.5) per 100,000 white males 25–44 years old in Melbourne . A 2009 health assessment for the National Football League (NFL) surveyed 1,625 former players and did not find any excess of renal disease . This group of athletes were known to frequently use anabolic steroids, particularly those retiring prior to the implementation of NFL anti-doping policies in 1989 .
The difficulty of making a comparison between the patients in the study by Herlitz et al.  and most athletes is that the NYC bodybuilders could be considered steroid dependent, a condition estimated to afflict about 30% of anabolic steroid users [27,28]. It is not at all clear whether the FSGS anabolic steroid risk should be based upon all users or only those that are considered dependent. Although the number of patients may be too small for the detection of rare kidney events, clinical studies of dependent anabolic steroids users have found “accelerated” coronary atherosclerosis and left ventricular muscle dysfunction but have not mentioned renal disease [27,28]. Nevertheless, if FSGS is increased among US anabolic steroid users, dependent or otherwise, the frequency of its recognition seems disproportionately low compared to the high rates of anabolic steroid exposure in US athletic communities [4,27,28]. In a 2019 scientific statement, the Endocrine Society recognized FSGS as a complication of anabolic steroid use, but considered it uncommon and less serious than cardiovascular disease .
Nearly all of the reports of nephrocalcinosis complicating bodybuilding have come from Brazil (2,3), but the use of up to 10,000 units a day of vitamin D is recommended in US and European muscle building e-magazines as a “steroid” that enhances muscle development [36,37]. With this level of advocacy, it is difficult to understand why nephrocalcinosis among bodybuilders appears to be so regionally localized, but it may be the method of delivery and the inflammatory response to the injections that contributes to the kidney disease.
The oil-based veterinary compounds are inexpensive and mainly used to add bulk to specific muscle groups. As was found in patient 15, the granulomatous oil containing reaction can act as a slowly releasing reservoir for the lipid soluble vitamins for months and possibly years . While the injection of high-dose veterinary vitamin compounds does not seem to have any role in Western bodybuilding, some European bodybuilders inject paraffin oils around muscles for their contouring effect, a practice that is also seen in some cosmetic surgeries [39,40]. The oils elicit a granulomatous reaction that is associated with hypercalcemia as a result of the local synthesis of active vitamin D [39,40]. Renal failure that is corrected when calcium and vitamin D levels are lowered is reported in most of these patients [39,40].
A major difficulty with the current study is that kidney disease was uncommon among gymnasium participants. This is inherent in the evaluation of any type of rare population event . FSGS is a useful example because of its controversial association with anabolic steroids. We estimate that a relationship between FSGS and anabolic steroids in our region would have required the identification of six FSGS patients over the 9.0 year collection period to be considered significantly different than its usual population frequency (Table 4). The threshold of six patients is needed despite what appears to be marked increases in ASIR with a simulated increase of even three or four FSGS patients.
The calculations emphasize that comparisons of the frequency of rare events that are typical of most kidney diseases can be misleading and require a measure of statistical uncertainty. In population studies, this uncertainty is usually achieved by confidence intervals, but because rare events produce very wide confidence intervals, the relevance of the estimates is frequently difficult to understand .
It is also a concern that our interest in bodybuilding-related kidney disease may have created an investigative bias, as the biopsy frequency for regular gymnasium participants was more than twice that of the general population. Since, however, the different biopsy frequencies uncovered essentially the same rates of disease, it is likely that, except for nephrocalcinosis, the kidney health of bodybuilders is not worse than that of other young men in the region.