Kidney stones can be a very painful disease for patients and physicians alike, with 1 in 11 people suffering from them. In recent decades, researchers have become concerned about the long-term complications of kidney stones, asking the question: are kidney stones associated with kidney disease?
Professor Zisman et al. summarize this in terms of epidemiological data, mechanisms of kidney injury and histopathology in an article published in the January 2016 issue of Kidney International.
The association between kidney stones and chronic kidney disease (CKD)
The association between kidney stones and CKD was first studied by Vupputuri et al. They analyzed 548 patients newly diagnosed with CKD and 514 age-, sex-, and race-matched local residents and found that nearly twice as many people with CKD had a history of kidney stones as controls.
Since then, researchers in various countries have conducted numerous studies with positive results regarding the association between kidney stones and CKD and end-stage renal disease (ESRD).
Ahmadi et al. studied 97 kidney stone patients undergoing extracorporeal shock wave lithotripsy and demonstrated a significant association between stone load and CKD, with a 20% increase in the risk of CKD for every 1 mm3 increase in stone volume.
The main determinants of decreased renal function are kidney loss (solitary kidney) and primary stones and stone-related systemic disease.
For example, cystine stones have a lower creatinine clearance than patients with other types of stones. Patients with kidney stones associated with intestinal disease, bariatric surgery, and renal tubular acidosis have lower creatinine clearance.
The main mechanisms of kidney damage caused by kidney stones
1. Recurrent obstruction caused by stones can lead to acute kidney injury (AKI), and recurrent AKI is a risk factor for CKD. In most cases, patients with unilateral obstruction do not develop symptoms of significant kidney injury like those of bilateral obstruction.
However, animal models suggest that unilateral obstruction can lead to increased tubular pressure, which in turn causes renal vasoconstriction, resulting in decreased renal blood flow, decreased glomerular filtration rate (GFR), and tissue ischemia. The persistent ischemic state leads to glomerulosclerosis, tubular atrophy, and interstitial fibrosis.
2. The results of Mayo’s study demonstrated that the risk factors for kidney stones in patients progressing to CKD are hypertension, diabetes, recurrent urinary tract infections, magnesium phosphate stones and treatment with allopurinol.
Although epidemiological data suggest a correlation between kidney stones and decreased renal function, this result is limited by differences in study samples, documentation and diagnostic principles, the high prevalence of comorbidities such as diabetes and metabolic syndrome, and the fact that almost all previous studies were retrospective.
In recent years, therefore, the Zisman team has used advanced surgical tools and histopathological techniques to evaluate the underlying mechanisms of renal injury in kidney stones.
The tissue for these studies was derived from percutaneous nephrolithotomy, and the findings revealed that many patients with kidney stones had renal papillary and cortical injury, with histopathological changes varying significantly with stone composition.
Kidney stones are classified as calcium oxalate stones, calcium phosphate stones, magnesium ammonium phosphate stones, uric acid stones, and stones associated with genetic disorders such as primary hyperoxaluria, cystinuria, adenosineuria, and Dent disease.
The most common stones are primary calcium oxalate stones, mainly associated with metabolic abnormalities such as primary urinary calcium increase, hypocitraturia, and increased urinary oxalate due to excessive intake.
The typical histopathological feature is Randall’s plaque, a calcium phosphate deposit in the renal interstitium without a surrounding inflammatory response, first described by Randall. In other causes of calcium oxalate stones, calcium is deposited in the Bellini ducts (intramedullary with collecting ducts) and extramedullary with collecting ducts, and there is a marked inflammatory response and subsequent fibrosis.
Calcium phosphate stones can cause Bellini duct occlusion, which in turn leads to tubular epithelial cell damage, detachment, peritubular fibrosis, and cortical damage. Magnesium ammonium phosphate stones are associated with bacterial infection and form in alkaline urine.
When stones grow rapidly, they form antler-shaped stones that fill the entire collecting system, causing significant obstruction and severely affecting kidney function. Large antler-type stones can cause renal papillary necrosis.
In Western countries, uric acid stones account for 8% to 10% of stones, and the trend is increasing with the aging of the population and obesity. Uric acid stones are formed in acidic urine, and uric acid crystals are deposited in the Bellini duct, the collecting ducts of the extramedullary zone, and the renal interstitium, causing an inflammatory response and fibrosis.
Primary hyperoxaluria is mainly due to oxalate crystals blocking the renal tubules without an inflammatory response. The mechanism of cystinuria injury is tubular blockage, leading to cellular damage, interstitial inflammation, glomerular loss, and dermal
mass fibrosis.
Adenine stones, like uric acid stones, are negative stones and therefore are often misdiagnosed as uric acid stones in the early stages, delaying treatment. the etiology of CKD is not known. renal tissue damage in Dent disease is typically characterized by renal calcinosis and interstitial fibrosis.
In summary, patients with kidney stones definitely have kidney disease and need to be alert to kidney injury.