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What is causing your chronic kidney disease?

Chronic kidney disease (CKD) is a condition that arises when an individual’s kidneys become damaged and can no longer function normally. Because the kidneys are responsible for filtering toxins, removing waste, and regulating fluid balance, damage to the kidneys can result in significant systemic symptoms and problems. Within the United States, it is estimated that more than 1 in 7 (~15%) of adults suffer from CKD. This means that approximately 37 million people in the United States have a variety of CKD. When left untreated, CKD tends to progress and result in worsening disease, potentially requiring dialysis or kidney transplantation. Additionally, there are a wide variety of conditions that cause CKD.

Diabetes

One condition that is commonly associated with, and thought to lead to development of CKD is diabetes. In fact, half of patients with Type 2 diabetes mellitus, and one-third with Type 1 diabetes will develop CKD. In these patients, it is unclear if their nephropathy is directly due to having diabetes, or if it is due to various comorbidities that may contribute to the renal damage present (hypertension, dyslipidemia, obesity, intra-renal vascular disease, etc). 

Diabetic CKD is thought of as being a microvascular disorder. Within the kidneys, arteries and veins branch out throughout the kidney and permit your blood to be filtered. In diabetic CKD, the microvasculature within the kidney becomes damaged; repeated exposure to elevated glucose (sugar) levels can lead to damage in the endothelial cells that line the vasculature, Some causes of diabetic CKD include: damage to vasculature due to production of reactive oxygen species, alterations in nutrient sensing pathways (mTOR), dysfunction of glomerular podocytes, inflammatory cell recruitment, and renal tubular dysfunction and fibrogenesis.

Hypertension

Hypertension and CKD are intricately linked, and often it is difficult to distinguish in a given patient  if hypertension is caused by CKD, or if CKD is caused by hypertension. The kidney is intricately involved in overall regulation of blood pressure, and as it becomes damaged, it becomes unable to further regulate blood pressure, resulting in worsening hypertension, resulting in a “detrimental feedback loop”. This is why individuals with an elevated blood pressure (greater than 180/100 mm Hg) have been shown to be 15 times more likely to develop end stage kidney disease. Providers treating individuals with hypertension and CKD will often suggest an alternative diet (especially focused on reducing salt intake), utilization of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker, and diuretic therapy. 

Genetic mutations

There is a wide variety of structural changes that can take place within cells when there are mutations in genes associated with cellular function. Because of this, there are a large number of genetic changes that can result in CKD. Some leading conditions that cause CKD and are known to have genetic factors involved in CKD disease progression include the presence of APOL1 risk alleles, sickle cell trait and disease, polycystic kidney disease, Alport syndrome, Congenital anomalies of the kidney and urinary tract, as well as other conditions that have familial inheritance patterns. It is important to learn if CKD has a genetic component in play, as that can significantly alter treatment and management options available. When there is a family history of CKD, it can often be helpful for patients to undergo genetic testing to determine if a genetic mutation is the cause of their condition.

Sociodemographic

There are many sociodemographic factors that can also affect incidence of CKD in a patient population. While these factors are multifactorial, some leading ones associated with increased risk of CKD are having an age >60 years, being of a nonwhite race, having a low income, or a low level of education. Many of these factors are also common in other conditions, and as such it can be difficult to distinguish the precise link between these and CKD.

Other health-related conditions

There are a wide variety of other medical conditions that can result in damage to the kidneys, and as such represent potential causes of CKD. These include (but are not limited to) autoimmune diseases, systemic infections, nephrotoxic medications, recurrent urinary tract infections, kidney stones, urinary tract obstruction, malignancy, obesity, reduced kidney mass (eg, nephrectomy, low birth weight), history of acute kidney injury, smoking, and intravenous drug use (eg, heroin, cocaine).

In summary, CKD is a condition that has a wide variety of causes. By knowing the precise cause of an individual’s CKD, it is possible to tailor treatment to ensure that patients are cared for in the best way possible. Any patients who are concerned that they may have CKD can consult with their provider who can provide recommendations on lifestyle changes, or potentially order laboratory testing to examine any factors they find concerning.

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