Primary Hyperoxaluria (PH) is a rare, inherited metabolic disorder that disrupts the body’s ability to properly metabolize glyoxylate, leading to excessive oxalate production. Normally, oxalate is the end product of metabolism, and it is eliminated in the urine but in people with PH, the overproduction leads to recurrent formation of stones in the kidneys, development of chronic kidney disease (CKD), and in severe cases, systemic oxalosis and end-stage kidney disease (Danese et al., 2023).
Despite its severity, PH is frequently misdiagnosed or diagnosed late, often mistaken for idiopathic kidney stone disease. Many patients experience years of unexplained pain, repeated kidney stone episodes, and urinary complications before receiving a correct diagnosis (Lawrence & Wattenberg, 2020).
“For years, doctors kept telling me to drink more water, that kidney stones were common. I started to feel like they didn’t believe me. But the pain kept coming, and I knew something was seriously wrong”
The path to diagnosis is long and frustrating
Symptoms, including recurrent kidney stones and urinary complications, often begin in childhood or adolescence but are frequently misattributed to common urinary tract issues (Goldfarb et al., 2023). This leads to years of unexplained pain and repeated emergency room visits before a definitive diagnosis is finally reached.
“I spent years bouncing between doctors, being told to drink more water or cut back on salt. No one considered that my kidney stones might be part of something much bigger” one patient explained.
Reaching a diagnosis can be emotionally and physically exhausting. Multiple invasive procedures, misdiagnoses, and failed treatments often precede genetic confirmation of PH. By the time many patients are diagnosed, significant kidney damage has already occurred, with up to 70% of adults and 40% of pediatric PH1 patients reaching end-stage renal disease at diagnosis (Lawrence & Wattenberg, 2020).
“I was diagnosed only after my kidneys had already started failing. If someone had caught this sooner, I might have been able to delay the damage” shared another patient.
Because many healthcare providers still view kidney stones as an isolated issue rather than a potential symptom of a rare metabolic disorder, diagnostic delays persist (OHF, 2020).
“Every time I got another stone, I thought, ‘This can’t be normal.’ But my doctors never mentioned PH until I had dozens of stones and significant kidney damage” a patient recounted.
For many individuals with PH, the first symptoms appear in early childhood or adolescence. The most common early sign is recurrent kidney stones, which cause severe pain, hematuria (blood in urine), and urinary tract complications (Goldfarb et al., 2023). However, because kidney stones are relatively common, healthcare providers often overlook PH as an underlying cause, leading to misdiagnosis and delays in proper treatment.
“I was only a child when I had my first kidney stone. My parents were told it was ‘bad luck’ and that it would pass. But then I had another one. And another. It wasn’t until my kidneys started failing that someone thought to check for PH” shared a patient diagnosed in their late teens.
The daily burden of disease
The hydration regimen affects all aspects of daily life
One of the most demanding aspects of PH management is the need for continuous hydration. Patients must drink between 3 and 6 liters of water per day to dilute urinary oxalate concentrations and prevent further kidney damage (Danese et al., 2023).
“It feels like I am drowning in water most days. I drink so much that my stomach hurts, but I know if I stop, I could end up in the hospital” said one patient.
Examples span from (Goldfarb et al., 2023; Danese et al., 2023; OHF, 2020):
- Patients must wake up multiple times at night to drink and urinate, leading to chronic sleep deprivation. The interrupted sleep cycle results in fatigue, reduced concentration, and long-term exhaustion, which can significantly impact daily activities, including work and school performance. Many patients report difficulty maintaining a structured sleep schedule, affecting their overall well-being.
- Work, school, and social events must be planned around access to fluids and restrooms. Hydration requirements mean patients must ensure they have constant access to water, making travel, long meetings, or classroom settings difficult. Students often require special accommodations, such as unrestricted bathroom privileges and frequent breaks, while adults must navigate workplace limitations, leading to job performance concerns and potential career sacrifices.
- Some patients struggle with nausea and bloating, making it difficult to drink the required amount. Large fluid volumes can cause gastrointestinal discomfort, and some patients experience electrolyte imbalances due to excessive water intake. Medical professionals sometimes recommend electrolyte monitoring and balancing hydration with proper salt intake to minimize these adverse effects, but the challenge remains significant for many.
- Dietary management is another challenge. Patients must avoid high-oxalate foods, such as spinach, nuts, chocolate, and certain fruits (OHF, 2020). However, “It’s frustrating when I tell people I have to avoid certain foods, and they say, ‘Oh, you can just cheat a little.’ They don’t realize that even one mistake could lead to another stone forming,” said one patient.
The difficulty of managing the pain induced by kidney stones
The pain is widely recognized as one of the most severe types of pain a person can endure, leaving patients with few effective management options. “The pain is unbearable. I feel like I am being stabbed from the inside, and there’s nothing I can do but wait for the stone to pass or go to the ER for pain relief,” one patient described. Pain management is challenging, as opioids are discouraged due to dependency risks, and nonsteroidal anti-inflammatory drugs (NSAIDs) can further harm kidney function. Many patients express frustration over the limited pain management options available. “I wish there were safer medications that worked for us. Every time I have a stone, I feel like I have to choose between unbearable pain and risking more damage to my kidneys,” shared one patient (Goldfarb et al., 2023).
Beyond physical symptoms, PH imposes a significant emotional and psychological burden
Studies (Goldfarb et al., 2023; Danese et al., 2023; OHF, 2020) show that:
- 85% of caregivers experience anxiety about their child’s future need for a transplant.
- 77% of patients worry about reaching end-stage kidney disease.
- Many individuals report social isolation due to hydration needs, dietary restrictions, and pain episodes. The necessity of constant hydration means patients often avoid long trips, social gatherings, or situations where access to water and restrooms may be limited. Dietary restrictions add another layer of isolation, making it difficult to share meals with friends or family without extensive planning. The pain and fatigue caused by kidney stones further restrict participation in physical activities and social events. “I feel like I’m constantly missing out—whether it’s skipping meals because I can’t eat what everyone else is having or staying home because I’m too exhausted from managing my hydration” shared one patient (Goldfarb et al., 2023).
“People see me and think I look fine, but they don’t see the nights I spend in pain, the exhaustion from waking up to drink water, or the fear of my kidneys failing” shared a patient with PH2.
Children and adolescents with PH struggle with frequent school absences, limitations in sports, and difficulties forming friendships. Adults with PH face career limitations due to frequent medical needs and uncertainty about their long-term health (OHF, 2020).
Treatment as a source of challenges – and hopes
Many patients feel that current treatments for PH are insufficient and burdensome, while emerging therapies offer new hope but remain inaccessible for some. “Dialysis keeps me alive, but it takes over my life. It’s exhausting, and I feel like I’m stuck in an endless cycle,” shared one patient undergoing frequent dialysis sessions (Goldfarb et al., 2023). The need for a liver-kidney transplant looms over many, with patients often feeling it is the only path forward despite its risks. “I used to think a transplant would be the end of my struggles. Now I know it’s just another chapter of this disease,” a transplant recipient explained (Lawrence & Wattenberg, 2020).
Patients who have accessed RNA interference (RNAi) therapies, such as Lumasiran and Nedosiran, have reported significant reductions in oxalate levels and newfound optimism. “For the first time in my life, I feel like I have some control over this disease. My oxalate levels are lower, and I’m not living in constant fear of kidney failure” said a patient currently on Lumasiran therapy (OHF, 2020). However, many are concerned about accessibility, with some expressing frustration at the high cost and limited availability of these treatments. “It’s heartbreaking knowing there’s something that could help me, but I don’t have access to it” said another patient waiting for approval (Danese et al., 2023).
Looking ahead, patients hope for earlier genetic screening, better physician awareness, and expanded treatment access. “I just want doctors to recognize PH sooner so that fewer people have to go through years of suffering like I did” one patient emphasized (Goldfarb et al., 2023). While new therapies are promising, the journey for PH patients is still one of advocacy, research, and ensuring that no one is left behind in the treatment revolution.
Conclusion
Living with PH is a relentless journey filled with uncertainty, lifestyle restrictions, and physical pain. The impact extends beyond the kidneys, affecting every aspect of daily life, from social interactions to professional aspirations. Despite these challenges, advancements in research and treatment are giving patients new hope. Continued efforts in early diagnosis, access to innovative treatments, and greater medical awareness are key to improving the quality of life for those living with PH.
“This disease has shaped my life in ways I never expected. But knowing that research is advancing and that I’m not alone in this fight keeps me moving forward.”
T4RD project is about unlocking potential in rare kidney disease research through a comprehensive harmonization and interoperability model
Focusing on primary hyperoxaluria (PH), Dent disease, and Cystinuria to enhance care pathways and improve patient outcomes across a broader spectrum of monogenic kidney stone disorders, this initiative is a collaboration powered by Novo Nordisk, ERKNet, and OxalEurope.
This involves establishing a European Rare Kidney Disease Patient Registry (ERKReg) and collaborating with the Hyperoxaluria Consortium for seamless data connection across ERKReg and PH-specific registries. The project aims to understand PH, Dent and Cystinuria diagnostic and referral pathways locally, measuring metrics like time-to-diagnosis, referring center numbers, and the percentage of patients diagnosed before ESKD. Educational activities target identified diagnostic pathway gaps at regional and local levels, incorporating KPI testing to assess initiative effectiveness and changes in clinical practice over time.
References
| Publication details | Key findings |
| Danese, M. D., Lindner, A., Lin, J., West, M., & Milliner, D. S. (2023). Qualitative Assessment of the Patient Experience of Primary Hyperoxaluria Type 1: An Observational Study. BMC Nephrology, 24(1), 145. https://doi.org/10.1186/s12882-023-03017-5 | Highlights the challenges in transitioning young adults with OI from peadiatric to adult healthcare services. Recommends structured transition programs to improve continuity of care and patient outcomes. Emphasises the need for multidisciplinary collaboration in adult care settings. |in transitioning young adults with OI from peadiatric to adult healthcare services. Recommends structured transition programs to improve continuity of care and patient outcomes. Emphasises the need for multidisciplinary collaboration in adult care settings. |
| Goldfarb, D. S., Modersitzki, F., Karafilidis, J., & Li-McLeod, J. (2023). Healthcare Utilization, Quality of Life, and Work Productivity Associated with Primary Hyperoxaluria: A Cross-Sectional Web-Based US Survey. Urolithiasis, 51(72). https://doi.org/10.1007/s00240-023-01436-4 | PH imposes a high healthcare burden, with frequent ER visits, substantial out-of-pocket costs, and reduced work and school productivity. Patients report significant mental health impacts, including anxiety and depression. |
| Lawrence, J. E., & Wattenberg, D. J. (2020). Primary Hyperoxaluria: The Patient and Caregiver Perspective. Clinical Journal of the American Society of Nephrology, 15(7), 909-911. https://doi.org/10.2215/CJN.13831119 | Caregivers and patients struggle with managing extreme hydration requirements, pain management, and uncertainty about long-term kidney health. Dialysis and transplant are viewed as inevitable outcomes without better treatments. |
| Oxalosis & Hyperoxaluria Foundation (OHF). (2020). The Voice of the Patient Report: Primary Hyperoxaluria. Externally Led Patient-Focused Drug Development Meeting Report. Retrieved from https://ohf.org/wp-content/uploads/2020/10/FINAL-VOP_Primary-HyperoxaluriaReport-compressed.pdf | Patients highlight the disruptive nature of hyperhydration, limited treatment options, and lack of disease awareness among healthcare providers. Calls for early genetic screening and access to new therapies. |