“The greatest evil is physical pain”
– Saint Augustine

Loin Pain Hematuria Syndrome (LPHS)

Loin Pain Hematuria Syndrome (LPHS) is a rare but very painful disorder involving the kidneys or urinary tract.  It is characterized by severe, often incapacitating loin (flank) pain that may be intermittent or constant, unilateral or bilateral, and accompanied by either microscopic or grossly bloody urine (hematuria). The frequency and duration of pain episodes vary from individual to individual. Patients with LPHS may initially present with grossly bloody urine or flank pain but most often both. Fortunately, in most cases LPHS is not associated with loss of kidney function or urinary tract infections. Unfortunately, the cause of LPHS in most cases is unknown.


See below for more information and treatment



Loin Pain Hematuria Syndrome (LPHS)



LPHS is a rare disorder that affects about 0.012% of the population, more often young females (up to 70%) than males, often caucasian, with the majority of patients developing symptoms by the third decade of life


Etiology, or Causes, of LPHS

Primary LPHS

LPHS is considered primary when it occurs without the presence of any damage to the filtering system of the kidneys (the glomeruli). Glomeruli are sets of looping blood vessels in nephrons—the tiny working units of the kidneys that filter wastes and remove extra fluid from the blood.  The cause(s) of primary LPHS is currently unknown but thought to possibly be related to either vascular disease of the kidney, spasm of the blood vessels in the kidneys with microinfarctions (stroke or heart attack-like vessel blockages), hypersensitivity, abnormal ureteral contractions (peristalsis), or deposition of calcium or uric acid microcrystals in the kidneys.


Secondary LPHS

LPHS is considered secondary when it occurs in the presence of glomerular pathology caused by another disorder, such as IgA nephropathy. IgA is an immunoglobulin, (antibody), a protein made by the immune system to protect the body from foreign substances such as bacteria or viruses.. IgA nephropathy, also known as Berger’s disease, is a kidney disease that occurs when IgA deposits inappropriately build up in the glomeruli, causing inflammation that damages the glomeruli, causing the kidneys to leak blood and protein into the urine.  IgA nephropathy can lead to impaired kidney function and ultimately may result in end-stage kidney disease (ESRD). Management of IgA nephropathy shoulc focus on controlling blood pressure to slow the progression of kidney disease. Additionally, support of the immune system is warrented.

For more information on IgA nephropathy: click here.


LPHS – Signs & Symptoms

The loin pain varies in duration and frequency; the duration can range from minutes to a constant ache and the frequency can vary from constant or only once or twice per year. In some cases the pain may radiate to the iliac fossa, anterior thigh or groin.


Physical exam and laboratory findings in LPHS vary buta most patients have unremarkable physical exams and the majority have normal kidney function, including creatinine clearance and serum creatinine.  Studies have shown that there are no abnormal 24-h urine concentrations of calcium, phosphorus, uric acid, oxalate and cystine. Coagulation studies in these patients are frequently normal, including partial thromboplastin time, prothrombin time, bleeding time, hematocrit and platelet count.


Hematuria can be either microscopic or macroscopic. Episodes of macroscopic hematuria are usually associated with worsening pain but in between episodes, the urine may show microscopic hematuria or in some patients, the hematuria clears completely even though the pain persists. The hematuria  in LPHS is typically glomerular in origin characterized by dysmorphic red cells with or without red blood cell casts. Typically there is no loss of protein in the urine.


Clinical Course:
The natural course of LPHS is not well known, but spontaneous resolution may occur. Some studies have shown that 25–50% of LPHS patients enter a period of spontaneous remission within 3–5 years.  In one study of 51 patients, LPHS resolved spontaneously in half the patients after several years (mean 3–5 years); the rest of the patients continued to have pain up to 17 years. LPHS generally does not cause secondary kidney injury or increase mortality.


Diagnosis of LPHS

The diagnosis of LPHS is one of exclusion, meaning that known causes of loin pain and bloody urine must first be excluded with extensive testing before assigning the diagnosis of LPHS. Many patients with LPHS remain undiagnosed for years, as patients often see multiple physicians in an effort to determine the cause of their pain before a proper diagnosis is made.


The exclusion of non-glomerular causes for the hematuria must be established first; the minimal criteria for LPHS include the presence of hematuria and pain for at least 6 months, which is proved not due to kidney stones (nephrolithiasis). A kidney biopsy may be needed to tell the difference between primary and secondary LPHS.


A variety of conditions must be considered when evaluating patients for LPHS. These include ureteral obstruction including kidney stones or tumor, kidney infection, benign or cancer kidney tumors, recurrent renal blood clots (thromboembolism), IgA nephropathy, blood vessel abnormalities and “Nutcracker syndrome”.


The Nutcracker syndrome refers to compression of the left renal vein, commonly between the aorta and the superior mesenteric artery, which leads to impaired blood flow and distention of the distal portion of the vein. Nutcracker syndrome is a clinical diagnosis of a complex of symptoms resembling those seen with LPHS, including hematuria, left flank pain and other fatigue symptoms. While rare, it is important to exclude nutcracker syndrome when evaluating patients for hematuria and left flank pain.

A variety of tests should be conducted in this process including urine cultures to rule out infection, a urinalysis should be done to check for glomerular disease. A cystoscopy and/or computed tomography (CT) can be done to check for kidney stones or other tumors and cysts. Angiography or CT angiography can be done to rule out A-V malformation and hemangioma whereas flexible ureteroscopy can be done to check for ureteral pathology. Coagulation studies should be ordered to check for problems with coagulopathy. Additionally, a psychiatric evaluation should be performed to assess for contributing issues surrounding chronic pain.


Treatment of LPHS

Because the condition of LPHS is still controversial with no consensus of validated diagnostic criteria or optimal treatment strategies, it is challenging to treat. Unless an underlying glomerular disease is treatable, treatment of both primary and secondary LPHS focuses on relieving the symptoms. Without a definite understanding of the underlying pathophysiological process in LPHS, the goal of treatment is focused on pain management. Since studies have shown that many LPHS patients have spontaneous remission, a gradual approach in treatment progressing from conservative management to more invasive measures is recommended.


Unfortunately, there is substantially more research published regarding invasive and surgical treatments of LPHS than conservative treatment. There is no definitive understaning as to the mechanism of pain in LPHS and it is likely that there are multiple mechanisms. As such, there is debate whether LPHS represents neuropathic pain or visceral pain, although there is evidence that visceral pain nevertheless has a component of neuropathic pain.

Based on theoretical mechanisms of the disorder, multiple medications have been tried to relieve LPHS pain, with varying degrees of success. Due to the rarity of the disorder there are no studies available that compare the success of different medications.  The following medications have demonstrated linited benefit in LPHS pain.
Patients are normally started with non-opioid analgesics but often progress to opioid analgesics with the goal of avoiding high-dose opioids. No sudies have been published that evaluate the effectiveness of one opioid over another. Due to the proposed neuropathic character of the pain, opioids with the most favorable activity against pain should be tried first, beginning with lower potency opioids. These include buprenorphine (Butrans or Belbuca), tapentadol (Nucynta), levorphanol and methadone. The use of short-acting vs. long-acting formulations should be determined bases on the patient’s pattern of pain.
Most opioids have limited effectiveness against neuropathic pain which can lead to higher doses. As such, it appears prudent to explore other agents with demonstrated effectiveness for neuropathic pain in effort to rely on opioids as little as possible.
ACE Inhibitors
There is limited evidence that angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker may reduce the frequency and severity of both gross hematuria and loin pain. The proposed mechanism is to reduce intraglomerular pressure by dilating efferent arterioles. The decreased pressure in turn decreases glomerular rupture and hematuria. This approach may be especially appropriate with patients demonstrating underlying thin glomerular basement membranes on kidney biopsy, suggested by findings of multiple renal tubules filled with red cells, apparently occluding the tubules. It is suggested that occlusion of a relatively small fraction of renal tubules could cause renal pain if back-leak of glomerular filtrate occurrs of sufficient magnitude to expand renal parenchymal volume and stretch the renal capsule.  One 1996 report of seven patients receiving enalapril for 7–48 months reported fewer severe episodes of both hematuria and pain.

Tadalafil (Cialis)

A 2015 case study reported on a 35-year-old female LPHS patient who routinely experienced episodes of completely incapacitating pain intensity of 2–4 hours duration. This patient was treated with a 5 mg oral dose of a crushed tadalafil (Cialis) tablet administered at the onset of the episodes of severe pain and the pain duration was reduced to less than 10 minutes. If the tadalafil was delayed until after onset, the original 2–4 hour course of agony occured. Taking tadalafil daily reduced the patient’s loin pain intensity, but not the exacerbations.


Tadalafil is a phosphodiesterase-V (PDE-V) inhibitor which is thought to reduce the severity of the ureteral ureter smooth spasm, a proposed mechanism for the severe episodic pain associated with LPHS. Other PDE-V inhibitors that may offer similar potential benefit include sildenafil (Viagra) and vardenafil (Levitra). An additional or alternative mechanism by which tadalafil might act is through reversal of transient intrarenal vasospasm.


Transcutaneous Electrical Nerve Stimulation (TENS)
Anecdotal references are made to the benefit of using Transcutaneous Electrical Nerve Stimulation (TENS) to reduce perception of the chronic, constant pain preceived by many with LPHS although there does not appear to specific studies undertaken to assess this.

Interventional and Surgical Procedures

Review of the specifics of interventional and surgical management of LPHS and their recommendations is beyond the scope of this treatise. The following interventional and surgical approaches have been tried with limited success.

Invasive Procedures

Intrathecal Opioid Therapy via an Implantable Pump

The use of an implantable pain pump system that deliver low-dose opioids directly into the spinal canal to act directly on the spinal cord and brain is a technique used for the management of a number of chronic pain conditions, most commonly chronic low back pain, to reduce reliance on oral opioids.


The pain pump system includes a small metal pump about the size of a hockey puck that is surgically implanted under the skin of the abdomen. Inside the pump is a reservoir that stores the medication and is refillable without the need for additional surgery. The pump delivers medication through a small plastic tube (catheter) that is surgically placed in the  fluid-filled space around the spinal cord called the subarachnoid or intrathecal space of the spine. This fluid, cerebrospinal fluid (CSF), flows around the spinal cord nourishing and protecting the brain and spinal cord. Delivering medication directly into the CSF allows medication access to pain centers and pain-related nerve pathways to reduce pain.


An implantable pain pump has been reported to successfully reduce pain in a patient with LPHS using long-term intrathecal morphine. Intrathecal opioid therapy may provide pain relief to allow for reduction or elimination of oral opioids.

Regional Nerve Blocks and Nerve Ablations

Regional nerve blocks have shown success in some cases of LPHS but they are not effective for long-term pain relief. Radiofrequency ablation of the renal sympathetic nerves has been successful but there is limited research on this technique.


Renal Denervation by Percutaneous Ablation

Case reports and small case series have shown percutaneous catheter-based renal nerve denervation (RDN) by ablation with radiofrequency energy to be successful for patients with LPHS. This technique has the advantage over surgical denervation (see below) of being catheter-based, safe, rapid, and minimally invasive. Early studies showed improvements in pain, disability, and quality of life from baseline to 6 months post-procedure. In a study published in 2018, most patients were initially able to either discontinue or significantly reduce their use of pain medications. However, the majority of patients on 9 month follow-up had recurrence of pain (although less than pre-procedural pain levels), indicating nerve regeneration. One-half of the patients underwent a second procedure between 9 and 15 months after the first procedure. One patient underwent the procedure a third time.


These studies suggest that percutaneous catheter-based renal nerve ablation with radiofrequency energy may be a treatment option for some patients with LPHS but long-term clinical studies are needed to fully evaluate the beneficial effects of RDN.


Of notable interest, patients in the 2018 study were found to exhibit heightened pain sensitivity as well as local loin-area hyperalgesia and allodynia, consistent with neuropathic pain.



One study has shown promising results for neuromodulation of the lumbar sympathetic plexus by using a low-frequency stimulation of  the autonomic system to control pain in four patients with LPHS. The study showed that patients had significant reduction in pain allowing them to return to activities of daily living with reduced use of analgesics. More experience is needed with this technique before it can be recommended for the management of LPHS.


Infusion of Capsaicin

Retrograde infusion of capsaicin into the ureter and renal pelvis has been performed with limited success in an attempt to block the sympathetic C fibers responsible for pain signal transmission. Reported complications include severe bladder pain, urinary tract infection, worsening kidney pain and, most importantly, deterioration of kidney function. Most experts have abandoned the use of capsaicin due to these potential complications necessitating a high rate of nephrectomy.

Surgical Procedures

Surgical Renal Denervation

Surgical denervation of the kidny involves stripping the kidney of the nerves that transmit pain. This can be achieved by several techniques including stripping the renal capsule from the kidney (capsulotomy), stripping the renal nerves from the renal artery (neurectomy), or by renal autotransplantation.


Surgical renal denervation has been found to be helpful for temporary complete relief from pain in some patients with LPHS, but relief was sustained for a maximum of 2 years. Three large series have reported results on renal denervation in LPHS. Reports for a total of 84 procedures performed in 65 patients with LPHS showed success rates ranging from 25 to 33% depending on the follow-up period, which varied from 8 to 54 months. The recurrence rate of ipsilateral (same side) pain was reported in up to 75% of the patients within an average of 6–11 months of the procedure. Mild postoperative complications of wound infection were reported in 8% of the procedures; otherwise, no serious complications were reported. The recurrence of pain is assumed to be due to nerve regeneration. Surgical renal denervation should not be performed in patients for whom renal autotransplantation is being considered due to the potential for dense scarring from the procedure that may complicate subsequent surgery.


Renal Auto-transplantation

Renal autotransplantation was first performed in 1982 and involves removing the kidney and inserting it to the ipsilateral iliac fossa to eliminate the pain of LPHS. It is believed that pain relief is due to the fact that all the nerves around the kidney are severed completely. It has been reported that 69% of kidney auto-transplant procedures resulted in significant pain relief for a follow-up period of 10 years, where most patients could be weaned off analgesics and back to normal daily activities. The longest reported period of pain relief following autotransplant is reported to be 21 years.


However, some studies have shown there is some recurrence of pain between 4 and 10 months. Additionally,  one study reported the incidence of postoperative complications associated with auto-transplantaion as high as 30% in 46 procedures in patients with LPHS. Complications included nephrectomy in four patients, infarction of the autotransplanted kidney, wound infection and nerve entrapment. Autotransplantation should not be first-line therapy and should be offered only to patients who are suitable candidates for surgery and have failed  extensive nonsurgical therapies.


Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement.


Genetic and Rare Diseases Information Center (GARD)

The Genetic and Rare Diseases Information Center (GARD) is a program of the National Center for Advancing Translational Sciences (NCATS) and is funded by two parts of the National Institutes of Health (NIH): NCATS and the National Human Genome Research Institute (NHGRI). GARD provides the public with access to current, reliable, and easy-to-understand information about rare or genetic diseases in English or Spanish.


  1. Loin pain hematuria syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program


Organizations Supporting LPHS

  1. National Kidney Federation (NKF)
    The Point
    Coach Road
    Notts S81 8BW
    United Kingdom
    Telephone: 0845 601 02 09
    Website: http://www.kidney.org.uk/

Social Networking Websites

  1. American Association of Kidney Patients
    3505 E. Frontage Rd., Suite 315
    Tampa, FL 33607-1796
    Toll-free: 800-749-2257
    Telephone: 813-636-8100
    Fax: 813-636-8122
    E-mail: info@aakp.org
    Website: http://www.aakp.org
  2. National Kidney Foundation
    30 East 33rd Street
    New York, NY 10016
    Toll-free: 800-622-9010
    Telephone: 212-889-2210
    Fax: 212-689-9261
    E-mail: info@kidney.org
    Website: https://www.kidney.org/


Loin Pain Hematuria Syndrome (LPHS) Overviews

  1. Loin pain hematuria syndrome. – PubMed – NCBI – 2014
  2. Loin pain hematuria syndrome – 2016
  3. Loin pain hematuria syndrome – 2006
  4. Severe unexplained loin pain (loin pain haematuria syndrome): management and long-term outcome. – PubMed – NCBI – 2007
  5. Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules. – PubMed – NCBI – 1996


  1. Chronic renal pain – An approach to investigation and management – 2018
  2. Nutcracker phenomenon presenting as loin pain haematuria syndrome – 2013
  3. What Each Clinical Anatomist Has to Know about Left Renal Vein Entrapment Syndrome (Nutcracker Syndrome) – A Review of the Most Important Findings – 2017
  4. Loin pain and haematuria syndrome: a somatoform disorder. – PubMed – NCBI – 1995
  5. Haematuria and loin pain, could this be tuberculosis? – 2015
  6. Loin pain hematuria syndrome-visceral or neuropathic pain syndrome? – PubMed – NCBI – 2012
  7. Loin pain hematuria syndrome: a psychiatric and surgical conundrum. – PubMed – NCBI – 2009


LPHSTreatment Overviews

  1. Loin Pain Haematuria Syndrome – A Narrative Review of Pain Management Strategies – 2016
  2. Loin pain hematuria syndrome-visceral or neuropathic pain syndrome? – PubMed – NCBI – 2012


LPHS – Treatment: Hypnotherapy

See: Hypnosis

  1. Hypnotherapy for the Management of Chronic Pain – 2007


LPHS Treatment – Pulsed Radiofrequency Ablation of Splanchnic Nerves

  1. A patient with loin hematuria syndrome and chronic flank pain treated with pulsed radiofrequency of the splanchnic nerves. – PubMed – NCBI 2013
  2. Renal Denervation in Patients With Loin Pain Hematuria Syndrome. – PubMed – NCBI – 2017
  3. Catheter-based renal denervation as therapy for chronic severe kidney-related pain. – PubMed – NCBI – 2018
  4. Successful Use of Renal Denervation in Patients With Loin Pain Hematuria Syndrome—The Regina Loin Pain Hematuria Syndrome Study – 2018


LPHS Treatment – Intrathecal Pump

  1. Loin pain hematuria syndrome: pain relief with intrathecal morphine. – PubMed – NCBI 1995


LPHS Treatment – Tadalafil (Cialis)

  1. Does this case hold the answer to one of the worse types of pain in medicine—that of loin pain haematuria syndrome (LPHS) – 2016
  2. Tamsulosin versus tadalafil as a medical expulsive therapy for distal ureteral stones – A prospective randomized study. – 2016


LPHS Treatment – Renal Denervation

  1. A patient with loin hematuria syndrome and chronic flank pain treated with pulsed radiofrequency of the splanchnic nerves. – PubMed – NCBI 2013
  2. Successful Use of Renal Denervation in Patients With Loin Pain Hematuria Syndrome—The Regina Loin Pain Hematuria Syndrome Study – 2018


LPHS Treatment – Spinal Cord Stimulation

  1. Lumbar sympathetic chain neuromodulation with implanted electrodes for long-term pain relief in loin pain haematuria syndrome. – PubMed – NCBI – 2009
  2. Spinal Cord Stimulation for Loin Pain Hematuria Syndrome: Clinical Report. – PubMed – NCBI – 2018


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