Rare Disease Report


Rare Diseases in Nephrology

Many rare diseases affect the kidneys and the urinary system, some limited to the urinary system itself (eg, membranous nephropathy), and some part of a condition (eg, Alport syndrome) that  causes additional symptoms in other organ systems. With varying degrees of severity, these diseases can affect different parts of the urinary system (kidney glomerulus, kidney tubules, urinary tract, etc) causing numerous symptoms.

Several of these diseases occur in the context of inflammation and autoimmune disease (eg, Goodpasture syndrome). Many rare types of vasculitis can also cause major kidney problems (eg, Henoch-Schönlein purpura nephritis).

Disorders of kidney development, kidney metabolism, or substance transport within the kidney also exist. Some are directly heritable diseases caused by genetic defects (eg, cystinuria). Rare  diseases can cause acute kidney damage (which may be repairable), but more often result in chronic kidney disease.

Diagnosis Challenges

Diagnosis of rare diseases in nephrology is often a challenge. Primary care physicians may not have experience with such conditions, and nephrologists may have seen only a few cases of a very rare disorder.

Diagnosis begins with a physical exam and taking a medical history. Disease symptoms vary, but can include swelling from water retention, blood in the urine, kidney pain, anemia, elevated blood pressure, kidney stones, and electrolyte imbalances. Some patients, however, do not experience any symptoms until their kidney damage is severe.

For many syndromes, symptoms begin gradually and worsen over time as the kidney becomes more and more damaged (eg, autosomal dominant polycystic kidney disease [ADPKD]). In other conditions, symptoms occur in flares (eg, kidney stones in cystinuria).

The medical history can be a diagnostic tool for some types of heritable rare diseases in nephrology. Even so, many patients with these diseases do not have family members with the condition.

Basic blood and urine tests are usually enough to diagnose the existence of kidney problems, but often not the specific condition. Imaging tests like ultrasounds or CT scans can help aid in diagnosis, as can a kidney biopsy to identify the specific disease process, but even these does not always lead to a definitive diagnosis.

Genetic tests may sometimes be helpful, particularly if a clinician already suspects a certain disease. After diagnosis, other members of the family may need to be tested as well, depending on the condition. Genetic testing of family members can help individuals make family planning decisions.

Online Resources

The Renal Association:

American Society of Nephrology Kidney Week:

Tests to measure kidney function and damage, and detect abnormalities:

Clinical practice guidelines for chronic kidney disease:

Genetic and Rare Diseases Information Center:

Clinical trials information:


Each disease requires a specific treatment strategy to, hopefully, reduce symptoms or slow the disease process. For most of these diseases, especially the many that have not received a great deal of research attention, no direct disease treatment exists.

However, even when direct disease treatment is unavailable, the symptoms and complications can sometimes be managed successfully, often with off-label medications that have not been approved for that particular disease. For example, although no specific medication is currently available to treat ADPKD, a patient can find relief with a blood pressure medication, a diuretic to remove excess fluid, a medication to treat anemia, or an antibiotic. An individual with kidney stones may benefit from lithotripsy. Those with severe kidney disease will eventually need dialysis or even kidney transplant, despite these remedies.

Some specific treatments for rare nephrology diseases include:

  • Eculizumab (Soliris) to target uncontrolled complement activation in aHUS
  • Cysteamine (Cystagon) to control excess cystine in cystinosis
  • Tiopronin (Thiola) to control the rate of cystine excretion in cystinuria
  • Tacrolimus (Prograf) to reduce rates of rejection in kidney transplant.

Clinical Trials

The following are a selection of ongoing clinical trials in rare nephrology diseases:

  • ADPKD: tolvaptan, lanreotide, everolimus
  • aHUS: OMS721, CCX168
  • Focal segmental glomerulosclerosis: losmapimod, RE-021
  • primary hyperoxaluria who are on dialysis: Oxalobacter formigenes

Advocacy Support and Information

Advocacy groups provide an important resource for patients, caregivers, and clinicians, offering introductory educational materials and practical advice for dealing with these conditions, as well as  more detailed information about recent research papers, current clinical trials, etc.

They also provide social support and avenues to learn from other families who have experience dealing with these diseases.

Below are some advocacy groups available for rare diseases in nephrology:
National Kidney Foundation:

The Atypical HUS Foundation:

Polycystic Kidney Disease Foundation:

Alport Syndome Foundation:

NephCure Kidney International:
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