As the one of the largest surgery center for HIV-positive patients in China, most of HIV positive urinary calculi patients in north China have came to our center for the cure. We found that the number of HIV-positive patients with stones had been increasing gradually in recent years. So we conducted the study to explore the reason and an possible way for prevention.
There are great differences in stone composition of different regions in the world. Amir's study of the stone composition in the Arab region showed that CaOMH is the most common one, accounting for almost 85% of all the patient. Tyson analyzed stones in Northern Ireland and also found that there was a high proportion of stones containing CaO (94.4%). Girişgen analyzed the stones of children in the central and western regions of Turkey, and found that CaOMH was the most common components, which might be related to diet habits. The prevalence of kidney stones in the United States in 2007–2010 is markedly higher than when last measured in 1988–1994.
In recent years, with the change in people's life and diet, the incidence rate of urinary calculi in China is also increasing[3, 10]. Because of the difference in geography, the composition of stones are also different. As known, the main composition of stones found in China is CaO. Ma systematically evaluated the multicenter studies in the north, East, central, South and southwest of China, and found that there were some differences in the material and element composition of urinary calculi in different regions. Zhang analyzed the composition of 3684 patients in the east of Shandong Province and found that CaO stone appeared most frequently. In Southwest China, the propotion of CaO stone is the highest, while in South China that of UA stone is the highest . In our study, we found that the CAO is the most one in the cohort, which is similliar to the propotions reported in HIV-negative patients before. As the cohort contains patients from both north and south of China, we still found certain propotion of UA which was also similliar to studies in HIV-negative patients.
UA is a common composition, accumulation about 40% in US, and 30%-40% in china.[3, 10] UA stone are already reported in many regions in large sample of Chinese data. In addition, the clinical features were highly correlated with stone type and anatomical location, but not with distribution area. It conforms to the current situation of stone in China.
Some studies suggested that higher serum UA level does not necessarily lead to UA stones. Patients with gout suppose to have higher incidence rate in UA urinary calculi. But Marchini found UA stones are the most common pure stone composition in patients with gout but 48% have nonuric acid stones. The serum UA level is just a cause or a risk factor for the formation of UA stones. Most have other metabolic riskfactors for stone formation. Yu and Gutman have reported that urinary stones were ascribed to hyperuricemia. The number of cases included in this study is relatively small, which may affect the results. Song also reported the relationship between serum UA level and metabolic abnormalities, among which 159 twins' differences in UA level were also related to metabolic abnormalities. And for HIV positive patients, there is study repoting the possible influence of HAART to induce the accumulation of UA. Pirro reported a study of 250 HIV-positive patients that after HAART treatment for at least 6 months, the serum UA level of the patients increased. The analysis indicated that it might be related to the insufficiency of endothelial cell function after HARRT. The study also found that the increase of serum UA level often occurred after receiving HAART, but it still needs a large number of prospective studies to verify. It can also be understood that the high level of UA in HIV positive group and urinary calculi may be related to the metabolic abnormality caused by antiviral treatment.
In our study, we found that the serum UA level of the HIV positive group is higher than that of HIV negative group, but there is no significant difference in the propotion of UA stones between two groups.
Because of the specific HARRT regime, evaluation of the stone composition of HIV-positive patient is essential.Acoording to previous studies, kidney stones were found to be more common in HIV positive patients taking protease inhibitors (PIs),and the main composition is the component of the medicine. This was mainly in the cases with indinavir, and this was also found in the cases with atazanavir. Other PIs such as nelfinavir, amprenavir, saquinavir, ritonavir and darunavir have also been reported to cause urolithiasis or to crystallize in urine. Ritonavir urolithiasis have been reported in several cases. Little is known regarding the pathophysiology of renal colic in patients taking PIs. Previous studies have suggested that impaired hepatic function could result in increased renal elimination, as hepatic metabolism is important for many of these PIs. Rockwood found Individuals with drug genetic predisposition to slower ritonavir-boosted atazanavir (ATZ/r) metabolism may increase the risk of stone formation due to higher ATZ/r-related levels. Previous studies have shown that impaired liver function may lead to increased renal clearance, because liver metabolism is important for many of these PIs. However, despite a large number of reports on HIV PIs related kidney stones, the formation mechanism of these kidney stones is not completely clear. In a retrospective study, only 28% of indinavir treated patients with kidney stones had stones containing indinavir. The other patients who did not take indiavir had stones containing calcium oxalate, ammonium urate and UA, and some had various metabolic abnormalities including low-carbon, high oxaluria and high calcium urine. Vassallo reported a case in which the debris found after lithotripsy was mainly Raltegravir. The plasma and urine concentrations of Raltegravir are at normal limits, making it unlikely that the dose will be inadequate. Only patients with a history of urolithiasis should be cautious with the prescription. But In our study, we analized 32 cases and we did not discover HAART medicine related stones composition.
And in the study we included that there were 21 people taking LPV / r, but no drug stone component was found. We suggested the that the reason might be related the HIV-positive group’s the basic normal liver and kidney functions. The metabolization in HIV-positive group may not be affected by the HAART. The occurrence of stone also may occur before HIV infection, because after HIV infection, the relevant examination was relatively in advance, so kidney stone was found earlier. It may indicate that we can make antiviral program for low-risk patients without considering the factors of PI drugs leading to stones.
The comparison of pure stones in our study, calcium oxalate dihydrate in HIV positive group was higher than that in negative group. There may be a higher risk of complications from taking antiretroviral drugs with urinary stones.
In addition, we also analized the CD4 count of HIV positive group. Although there were 4 patients less than 200, no serious urinary tract infection was found after the operation, which may be related to the preoperative full evaluation, control of operation time and the prevention and application of antibiotics. In terms of operation mode, the HIV group and the normal group were mainly operated by ureteroscopy with less trauma, and PCNL was used relatively small, but it may also be related to the relatively small number of cases. The next step may be to compare the operation outcome.
However, this case-control trial increases the possibility of prognostic differences between HIV and negative groups. There was no significant difference in age, gender and BMI. The advantages of our study include the comparison of stone composition. However there is still a need for further study and design of randomized controlled trials. We should have more patients to go in for studies. The study will be continued in the future.
We have determined to pay more attention to the HIV-positive patients with urinary calculi. Above all, we need to collaborate more details to analyze. At last, this study retrospective analysis of single center cases in our hospital, case-control study of stone composition analysis for patients with HIV infection and normal patients, hoping to observe some situations, and provide some data support for clinical early prevention.