Among 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. Injecting patients can present with reversible acute kidney injury, but once nephrocalcinosis is established, the outcome appears ominous with a risk of ESRD that from the limited Kurdistan experience may approach 50% within 2 years after diagnosis (3,4).
ATN was the most common renal disease encountered among our bodybuilders. We commonly see elevated creatinine levels in laborers and soldiers during the summer months, but these patients are treated on the basis of clinical and laboratory findings and are not biopsied. Patients with evidence of AKI are usually biopsied if there is no apparent underlying cause, and these biopsied patients comprise our estimates of the incidence of ATN in the general 15-39 year old male population.
Data on the rates of AKI among young males is not readily available, but the 1996 study by Liano et al. from Madrid  reports an annual clinical incidence for ATN of 8.8 patients per 100,000 persons in which the average patient age was 63 ± 17 years. The proportion of AKI patients under 44 years old with no co-morbid disease has been estimated at 10.5% . That frequency would calculate to an annual incidence of 0.9 (0.6 to 1.2) young Madrid patients per 100,000 residents . While 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, the difference is not particularly great and shows, even with the disparity between clinical and biopsy diagnoses, that AKI is uncommon among otherwise healthy young males.
Two of the ATN patients that we report were new to bodybuildng and presented with muscle pain and evidence of rhabdomyolysis. This is referred to as exertional muscle injury and is attributed to microscopic muscle damage [16,17]. It is sometimes accompanied by myoglobinuria that is of concern because of the association of myoglobinuria with kidney injury .
The biopsies of ATN among the 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 [18,19,20], and serum calcium levels were within the normal range. 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 for calcium .
Most of the patients with ATN in our current study had histologic evidence of chronic injury. 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. [21,22]. Whether the risk applies to younger patients is not clear, but baseline normal renal function associates with a decreased risk of ESRD over time [22,23]. 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 in bodybuilders has been a TIN resembling a drug-type allergy in which the renal failure resolves when supplements are discontinued [24,25]. 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.
For the level of anabolic steroid use practiced in the region that includes multiple drug regimens in 21% of experienced bodybuilders, the incidence of FSGS could not be considered any greater than that of the general population. While there is experimental evidence that anabolic steroids may be toxic to podocytes [7,8,9], the primary association between anabolic steroids and FSGS comes from case studies and particularly the 2011 report by Herlitz et al.  of ten bodybuilders 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. A similar 2018 paper by El-Reshaid et al. , reported FSGS among eight "elite" anabolic steroid using bodybuilders from Kuwait that were collected over a period of five years.
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. (8) would then calculate to an annual ASIR of 2.9 (1.0 to 4.8) patients per 100,000 steroid users.
The incidence of FSGS has been estimated from biopsy series from Olmstead County, Minnesota and from Melbourne, Australia [30,31]. 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 . The population of Kuwait is similar to Iraqi Kurdistan, and the biopsy frequency of 1.6 cases of FSGS per year among anabolic steroid using bodybuilders reported by El-Reshaid et al.  would certainly seem excessive, but a relationship to the general incidence of FSGS and the chance of episodic random clustering among bodybuilders must also be considered.
One difficulty of making a comparison between most bodybuilders and the patients reported by Herlitz et al.  and El-Reshaid et al.  is that the NYC and Kuwaiti bodybuilders would be considered steroid dependent, a condition estimated to afflict about 30% of anabolic steroid users but probably not a factor in Kurdistan [27,28]. It is not at all clear whether the FSGS anabolic steroid risk should be based upon all users or only those 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 [5,27,28,32,33]. 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 (2,3,4), 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 [34,35]. 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 that contributes to the 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 [37,38]. The oils elicit a granulomatous reaction that is associated with hypercalcemia as a result of the local synthesis of active vitamin D [36,37]. Renal failure that is corrected when calcium and vitamin D levels are lowered is reported in many of these patients [4,36,37].
The limitations of our current study include the accuracy of estimating gymnasium participation and supplement use. Such estimates necessarily require sampling and self reporting since it is not possible to directly censor these factors. Our bodybuilding estimates were derived from data provided by large regional gymnasiums, and queries about supplement use were made only in Sulaimania. Data could be biased towards large gymnasiums and single city supplement use, but reviewing officials stated that the findings reflected their experience and that little variation would be expected in the relatively homogeneous Kurdistan region.
The principal limitation was that kidney disease was uncommon among gymnasium participants. This is inherent in the evaluation of any type of rare disease where events may cluster or go undetected for extended periods of time . 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 seven FSGS patients over the 9.0 year collection period to be considered significantly different than its usual population frequency (Table 4). The threshold of seven 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 is usually achieved by confidence intervals, but because rare events produce very wide confidence intervals, the relevance of the estimates can be 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.